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Cloning – Wikipedia

Posted: December 7, 2016 at 5:44 am

In biology, cloning is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments (molecular cloning), cells (cell cloning), or organisms. The term also refers to the production of multiple copies of a product such as digital media or software.

The term clone, invented by J. B. S. Haldane, is derived from the Ancient Greek word kln, “twig”, referring to the process whereby a new plant can be created from a twig. In horticulture, the spelling clon was used until the twentieth century; the final e came into use to indicate the vowel is a “long o” instead of a “short o”.[1][2] Since the term entered the popular lexicon in a more general context, the spelling clone has been used exclusively.

In botany, the term lusus was traditionally used.[3]:21, 43

Cloning is a natural form of reproduction that has allowed life forms to spread for more than 50 thousand years. It is the reproduction method used by plants, fungi, and bacteria, and is also the way that clonal colonies reproduce themselves.[4][5] Examples of these organisms include blueberry plants, hazel trees, the Pando trees,[6][7] the Kentucky coffeetree, Myricas, and the American sweetgum.

Molecular cloning refers to the process of making multiple molecules. Cloning is commonly used to amplify DNA fragments containing whole genes, but it can also be used to amplify any DNA sequence such as promoters, non-coding sequences and randomly fragmented DNA. It is used in a wide array of biological experiments and practical applications ranging from genetic fingerprinting to large scale protein production. Occasionally, the term cloning is misleadingly used to refer to the identification of the chromosomal location of a gene associated with a particular phenotype of interest, such as in positional cloning. In practice, localization of the gene to a chromosome or genomic region does not necessarily enable one to isolate or amplify the relevant genomic sequence. To amplify any DNA sequence in a living organism, that sequence must be linked to an origin of replication, which is a sequence of DNA capable of directing the propagation of itself and any linked sequence. However, a number of other features are needed, and a variety of specialised cloning vectors (small piece of DNA into which a foreign DNA fragment can be inserted) exist that allow protein production, affinity tagging, single stranded RNA or DNA production and a host of other molecular biology tools.

Cloning of any DNA fragment essentially involves four steps[8]

Although these steps are invariable among cloning procedures a number of alternative routes can be selected; these are summarized as a cloning strategy.

Initially, the DNA of interest needs to be isolated to provide a DNA segment of suitable size. Subsequently, a ligation procedure is used where the amplified fragment is inserted into a vector (piece of DNA). The vector (which is frequently circular) is linearised using restriction enzymes, and incubated with the fragment of interest under appropriate conditions with an enzyme called DNA ligase. Following ligation the vector with the insert of interest is transfected into cells. A number of alternative techniques are available, such as chemical sensitivation of cells, electroporation, optical injection and biolistics. Finally, the transfected cells are cultured. As the aforementioned procedures are of particularly low efficiency, there is a need to identify the cells that have been successfully transfected with the vector construct containing the desired insertion sequence in the required orientation. Modern cloning vectors include selectable antibiotic resistance markers, which allow only cells in which the vector has been transfected, to grow. Additionally, the cloning vectors may contain colour selection markers, which provide blue/white screening (alpha-factor complementation) on X-gal medium. Nevertheless, these selection steps do not absolutely guarantee that the DNA insert is present in the cells obtained. Further investigation of the resulting colonies must be required to confirm that cloning was successful. This may be accomplished by means of PCR, restriction fragment analysis and/or DNA sequencing.

Cloning a cell means to derive a population of cells from a single cell. In the case of unicellular organisms such as bacteria and yeast, this process is remarkably simple and essentially only requires the inoculation of the appropriate medium. However, in the case of cell cultures from multi-cellular organisms, cell cloning is an arduous task as these cells will not readily grow in standard media.

A useful tissue culture technique used to clone distinct lineages of cell lines involves the use of cloning rings (cylinders).[9] In this technique a single-cell suspension of cells that have been exposed to a mutagenic agent or drug used to drive selection is plated at high dilution to create isolated colonies, each arising from a single and potentially clonal distinct cell. At an early growth stage when colonies consist of only a few cells, sterile polystyrene rings (cloning rings), which have been dipped in grease, are placed over an individual colony and a small amount of trypsin is added. Cloned cells are collected from inside the ring and transferred to a new vessel for further growth.

Somatic-cell nuclear transfer, known as SCNT, can also be used to create embryos for research or therapeutic purposes. The most likely purpose for this is to produce embryos for use in stem cell research. This process is also called “research cloning” or “therapeutic cloning.” The goal is not to create cloned human beings (called “reproductive cloning”), but rather to harvest stem cells that can be used to study human development and to potentially treat disease. While a clonal human blastocyst has been created, stem cell lines are yet to be isolated from a clonal source.[10]

Therapeutic cloning is achieved by creating embryonic stem cells in the hopes of treating diseases such as diabetes and Alzheimer’s. The process begins by removing the nucleus (containing the DNA) from an egg cell and inserting a nucleus from the adult cell to be cloned.[11] In the case of someone with Alzheimer’s disease, the nucleus from a skin cell of that patient is placed into an empty egg. The reprogrammed cell begins to develop into an embryo because the egg reacts with the transferred nucleus. The embryo will become genetically identical to the patient.[11] The embryo will then form a blastocyst which has the potential to form/become any cell in the body.[12]

The reason why SCNT is used for cloning is because somatic cells can be easily acquired and cultured in the lab. This process can either add or delete specific genomes of farm animals. A key point to remember is that cloning is achieved when the oocyte maintains its normal functions and instead of using sperm and egg genomes to replicate, the oocyte is inserted into the donors somatic cell nucleus.[13] The oocyte will react on the somatic cell nucleus, the same way it would on sperm cells.[13]

The process of cloning a particular farm animal using SCNT is relatively the same for all animals. The first step is to collect the somatic cells from the animal that will be cloned. The somatic cells could be used immediately or stored in the laboratory for later use.[13] The hardest part of SCNT is removing maternal DNA from an oocyte at metaphase II. Once this has been done, the somatic nucleus can be inserted into an egg cytoplasm.[13] This creates a one-cell embryo. The grouped somatic cell and egg cytoplasm are then introduced to an electrical current.[13] This energy will hopefully allow the cloned embryo to begin development. The successfully developed embryos are then placed in surrogate recipients, such as a cow or sheep in the case of farm animals.[13]

SCNT is seen as a good method for producing agriculture animals for food consumption. It successfully cloned sheep, cattle, goats, and pigs. Another benefit is SCNT is seen as a solution to clone endangered species that are on the verge of going extinct.[13] However, stresses placed on both the egg cell and the introduced nucleus can be enormous, which led to a high loss in resulting cells in early research. For example, the cloned sheep Dolly was born after 277 eggs were used for SCNT, which created 29 viable embryos. Only three of these embryos survived until birth, and only one survived to adulthood.[14] As the procedure could not be automated, and had to be performed manually under a microscope, SCNT was very resource intensive. The biochemistry involved in reprogramming the differentiated somatic cell nucleus and activating the recipient egg was also far from being well-understood. However, by 2014 researchers were reporting cloning success rates of seven to eight out of ten[15] and in 2016, a Korean Company Sooam Biotech was reported to be producing 500 cloned embryos per day.[16]

In SCNT, not all of the donor cell’s genetic information is transferred, as the donor cell’s mitochondria that contain their own mitochondrial DNA are left behind. The resulting hybrid cells retain those mitochondrial structures which originally belonged to the egg. As a consequence, clones such as Dolly that are born from SCNT are not perfect copies of the donor of the nucleus.

Organism cloning (also called reproductive cloning) refers to the procedure of creating a new multicellular organism, genetically identical to another. In essence this form of cloning is an asexual method of reproduction, where fertilization or inter-gamete contact does not take place. Asexual reproduction is a naturally occurring phenomenon in many species, including most plants (see vegetative reproduction) and some insects. Scientists have made some major achievements with cloning, including the asexual reproduction of sheep and cows. There is a lot of ethical debate over whether or not cloning should be used. However, cloning, or asexual propagation,[17] has been common practice in the horticultural world for hundreds of years.

The term clone is used in horticulture to refer to descendants of a single plant which were produced by vegetative reproduction or apomixis. Many horticultural plant cultivars are clones, having been derived from a single individual, multiplied by some process other than sexual reproduction.[18] As an example, some European cultivars of grapes represent clones that have been propagated for over two millennia. Other examples are potato and banana.[19]Grafting can be regarded as cloning, since all the shoots and branches coming from the graft are genetically a clone of a single individual, but this particular kind of cloning has not come under ethical scrutiny and is generally treated as an entirely different kind of operation.

Many trees, shrubs, vines, ferns and other herbaceous perennials form clonal colonies naturally. Parts of an individual plant may become detached by fragmentation and grow on to become separate clonal individuals. A common example is in the vegetative reproduction of moss and liverwort gametophyte clones by means of gemmae. Some vascular plants e.g. dandelion and certain viviparous grasses also form seeds asexually, termed apomixis, resulting in clonal populations of genetically identical individuals.

Clonal derivation exists in nature in some animal species and is referred to as parthenogenesis (reproduction of an organism by itself without a mate). This is an asexual form of reproduction that is only found in females of some insects, crustaceans, nematodes,[20] fish (for example the hammerhead shark[21]), the Komodo dragon[21] and lizards. The growth and development occurs without fertilization by a male. In plants, parthenogenesis means the development of an embryo from an unfertilized egg cell, and is a component process of apomixis. In species that use the XY sex-determination system, the offspring will always be female. An example is the little fire ant (Wasmannia auropunctata), which is native to Central and South America but has spread throughout many tropical environments.

Artificial cloning of organisms may also be called reproductive cloning.

Hans Spemann, a German embryologist was awarded a Nobel Prize in Physiology or Medicine in 1935 for his discovery of the effect now known as embryonic induction, exercised by various parts of the embryo, that directs the development of groups of cells into particular tissues and organs. In 1928 he and his student, Hilde Mangold, were the first to perform somatic-cell nuclear transfer using amphibian embryos one of the first moves towards cloning.[22]

Reproductive cloning generally uses “somatic cell nuclear transfer” (SCNT) to create animals that are genetically identical. This process entails the transfer of a nucleus from a donor adult cell (somatic cell) to an egg from which the nucleus has been removed, or to a cell from a blastocyst from which the nucleus has been removed.[23] If the egg begins to divide normally it is transferred into the uterus of the surrogate mother. Such clones are not strictly identical since the somatic cells may contain mutations in their nuclear DNA. Additionally, the mitochondria in the cytoplasm also contains DNA and during SCNT this mitochondrial DNA is wholly from the cytoplasmic donor’s egg, thus the mitochondrial genome is not the same as that of the nucleus donor cell from which it was produced. This may have important implications for cross-species nuclear transfer in which nuclear-mitochondrial incompatibilities may lead to death.

Artificial embryo splitting or embryo twinning, a technique that creates monozygotic twins from a single embryo, is not considered in the same fashion as other methods of cloning. During that procedure, an donor embryo is split in two distinct embryos, that can then be transferred via embryo transfer. It is optimally performed at the 6- to 8-cell stage, where it can be used as an expansion of IVF to increase the number of available embryos.[24] If both embryos are successful, it gives rise to monozygotic (identical) twins.

Dolly, a Finn-Dorset ewe, was the first mammal to have been successfully cloned from an adult somatic cell. Dolly was formed by taking a cell from the udder of her 6-year old biological mother.[25] Dolly’s embryo was created by taking the cell and inserting it into a sheep ovum. It took 434 attempts before an embryo was successful.[26] The embryo was then placed inside a female sheep that went through a normal pregnancy.[27] She was cloned at the Roslin Institute in Scotland by British scientists Sir Ian Wilmut and Keith Campbell and lived there from her birth in 1996 until her death in 2003 when she was six. She was born on 5 July 1996 but not announced to the world until 22 February 1997.[28] Her stuffed remains were placed at Edinburgh’s Royal Museum, part of the National Museums of Scotland.[29]

Dolly was publicly significant because the effort showed that genetic material from a specific adult cell, programmed to express only a distinct subset of its genes, can be reprogrammed to grow an entirely new organism. Before this demonstration, it had been shown by John Gurdon that nuclei from differentiated cells could give rise to an entire organism after transplantation into an enucleated egg.[30] However, this concept was not yet demonstrated in a mammalian system.

The first mammalian cloning (resulting in Dolly the sheep) had a success rate of 29 embryos per 277 fertilized eggs, which produced three lambs at birth, one of which lived. In a bovine experiment involving 70 cloned calves, one-third of the calves died young. The first successfully cloned horse, Prometea, took 814 attempts. Notably, although the first[clarification needed] clones were frogs, no adult cloned frog has yet been produced from a somatic adult nucleus donor cell.

There were early claims that Dolly the sheep had pathologies resembling accelerated aging. Scientists speculated that Dolly’s death in 2003 was related to the shortening of telomeres, DNA-protein complexes that protect the end of linear chromosomes. However, other researchers, including Ian Wilmut who led the team that successfully cloned Dolly, argue that Dolly’s early death due to respiratory infection was unrelated to deficiencies with the cloning process. This idea that the nuclei have not irreversibly aged was shown in 2013 to be true for mice.[31]

Dolly was named after performer Dolly Parton because the cells cloned to make her were from a mammary gland cell, and Parton is known for her ample cleavage.[32]

The modern cloning techniques involving nuclear transfer have been successfully performed on several species. Notable experiments include:

Human cloning is the creation of a genetically identical copy of a human. The term is generally used to refer to artificial human cloning, which is the reproduction of human cells and tissues. It does not refer to the natural conception and delivery of identical twins. The possibility of human cloning has raised controversies. These ethical concerns have prompted several nations to pass legislature regarding human cloning and its legality.

Two commonly discussed types of theoretical human cloning are therapeutic cloning and reproductive cloning. Therapeutic cloning would involve cloning cells from a human for use in medicine and transplants, and is an active area of research, but is not in medical practice anywhere in the world, as of 2014. Two common methods of therapeutic cloning that are being researched are somatic-cell nuclear transfer and, more recently, pluripotent stem cell induction. Reproductive cloning would involve making an entire cloned human, instead of just specific cells or tissues.[57]

There are a variety of ethical positions regarding the possibilities of cloning, especially human cloning. While many of these views are religious in origin, the questions raised by cloning are faced by secular perspectives as well. Perspectives on human cloning are theoretical, as human therapeutic and reproductive cloning are not commercially used; animals are currently cloned in laboratories and in livestock production.

Advocates support development of therapeutic cloning in order to generate tissues and whole organs to treat patients who otherwise cannot obtain transplants,[58] to avoid the need for immunosuppressive drugs,[57] and to stave off the effects of aging.[59] Advocates for reproductive cloning believe that parents who cannot otherwise procreate should have access to the technology.[60]

Opponents of cloning have concerns that technology is not yet developed enough to be safe[61] and that it could be prone to abuse (leading to the generation of humans from whom organs and tissues would be harvested),[62][63] as well as concerns about how cloned individuals could integrate with families and with society at large.[64][65]

Religious groups are divided, with some opposing the technology as usurping “God’s place” and, to the extent embryos are used, destroying a human life; others support therapeutic cloning’s potential life-saving benefits.[66][67]

Cloning of animals is opposed by animal-groups due to the number of cloned animals that suffer from malformations before they die,[68][69] and while food from cloned animals has been approved by the US FDA,[70][71] its use is opposed by groups concerned about food safety.[72][73][74]

Cloning, or more precisely, the reconstruction of functional DNA from extinct species has, for decades, been a dream. Possible implications of this were dramatized in the 1984 novel Carnosaur and the 1990 novel Jurassic Park.[75][76] The best current cloning techniques have an average success rate of 9.4 percent[77] (and as high as 25 percent[31]) when working with familiar species such as mice,[note 1] while cloning wild animals is usually less than 1 percent successful.[80] Several tissue banks have come into existence, including the “Frozen Zoo” at the San Diego Zoo, to store frozen tissue from the world’s rarest and most endangered species.[75][81][82]

In 2001, a cow named Bessie gave birth to a cloned Asian gaur, an endangered species, but the calf died after two days. In 2003, a banteng was successfully cloned, followed by three African wildcats from a thawed frozen embryo. These successes provided hope that similar techniques (using surrogate mothers of another species) might be used to clone extinct species. Anticipating this possibility, tissue samples from the last bucardo (Pyrenean ibex) were frozen in liquid nitrogen immediately after it died in 2000. Researchers are also considering cloning endangered species such as the giant panda and cheetah.

In 2002, geneticists at the Australian Museum announced that they had replicated DNA of the thylacine (Tasmanian tiger), at the time extinct for about 65 years, using polymerase chain reaction.[83] However, on 15 February 2005 the museum announced that it was stopping the project after tests showed the specimens’ DNA had been too badly degraded by the (ethanol) preservative. On 15 May 2005 it was announced that the thylacine project would be revived, with new participation from researchers in New South Wales and Victoria.

In January 2009, for the first time, an extinct animal, the Pyrenean ibex mentioned above was cloned, at the Centre of Food Technology and Research of Aragon, using the preserved frozen cell nucleus of the skin samples from 2001 and domestic goat egg-cells. The ibex died shortly after birth due to physical defects in its lungs.[84]

One of the most anticipated targets for cloning was once the woolly mammoth, but attempts to extract DNA from frozen mammoths have been unsuccessful, though a joint Russo-Japanese team is currently working toward this goal. In January 2011, it was reported by Yomiuri Shimbun that a team of scientists headed by Akira Iritani of Kyoto University had built upon research by Dr. Wakayama, saying that they will extract DNA from a mammoth carcass that had been preserved in a Russian laboratory and insert it into the egg cells of an African elephant in hopes of producing a mammoth embryo. The researchers said they hoped to produce a baby mammoth within six years.[85][86] It was noted, however that the result, if possible, would be an elephant-mammoth hybrid rather than a true mammoth.[87] Another problem is the survival of the reconstructed mammoth: ruminants rely on a symbiosis with specific microbiota in their stomachs for digestion.[87]

Scientists at the University of Newcastle and University of New South Wales announced in March 2013 that the very recently extinct gastric-brooding frog would be the subject of a cloning attempt to resurrect the species.[88]

Many such “de-extinction” projects are described in the Long Now Foundation’s Revive and Restore Project.[89]

After an eight-year project involving the use of a pioneering cloning technique, Japanese researchers created 25 generations of healthy cloned mice with normal lifespans, demonstrating that clones are not intrinsically shorter-lived than naturally born animals.[31][90]

In a detailed study released in 2016 and less detailed studies by others suggest that once cloned animals get past the first month or two of life they are generally healthy. However, early pregnancy loss and neonatal losses are still greater with cloning than natural conception or assisted reproduction (IVF). Current research endeavors are attempting to overcome this problem.[32]

In an article in the 8 November 1993 article of Time, cloning was portrayed in a negative way, modifying Michelangelo’s Creation of Adam to depict Adam with five identical hands. Newsweek’s 10 March 1997 issue also critiqued the ethics of human cloning, and included a graphic depicting identical babies in beakers.

Cloning is a recurring theme in a wide variety of contemporary science fiction, ranging from action films such as Jurassic Park (1993), The 6th Day (2000), Resident Evil (2002), Star Wars (2002) and The Island (2005), to comedies such as Woody Allen’s 1973 film Sleeper.[91]

Science fiction has used cloning, most commonly and specifically human cloning, due to the fact that it brings up controversial questions of identity.[92][93]A Number is a 2002 play by English playwright Caryl Churchill which addresses the subject of human cloning and identity, especially nature and nurture. The story, set in the near future, is structured around the conflict between a father (Salter) and his sons (Bernard 1, Bernard 2, and Michael Black) two of whom are clones of the first one. A Number was adapted by Caryl Churchill for television, in a co-production between the BBC and HBO Films.[94]

A recurring sub-theme of cloning fiction is the use of clones as a supply of organs for transplantation. The 2005 Kazuo Ishiguro novel Never Let Me Go and the 2010 film adaption[95] are set in an alternate history in which cloned humans are created for the sole purpose of providing organ donations to naturally born humans, despite the fact that they are fully sentient and self-aware. The 2005 film The Island[96] revolves around a similar plot, with the exception that the clones are unaware of the reason for their existence.

The use of human cloning for military purposes has also been explored in several works. Star Wars portrays human cloning in Clone Wars.[97]

The exploitation of human clones for dangerous and undesirable work was examined in the 2009 British science fiction film Moon.[98] In the futuristic novel Cloud Atlas and subsequent film, one of the story lines focuses on a genetically-engineered fabricant clone named Sonmi~451 who is one of millions raised in an artificial “wombtank,” destined to serve from birth. She is one of thousands of clones created for manual and emotional labor; Sonmi herself works as a server in a restaurant. She later discovers that the sole source of food for clones, called ‘Soap’, is manufactured from the clones themselves.[99]

Cloning has been used in fiction as a way of recreating historical figures. In the 1976 Ira Levin novel The Boys from Brazil and its 1978 film adaptation, Josef Mengele uses cloning to create copies of Adolf Hitler.[100]

In 2012, a Japanese television show named “Bunshin” was created. The story’s main character, Mariko, is a woman studying child welfare in Hokkaido. She grew up always doubtful about the love from her mother, who looked nothing like her and who died nine years before. One day, she finds some of her mother’s belongings at a relative’s house, and heads to Tokyo to seek out the truth behind her birth. She later discovered that she was a clone.[101]

In the 2013 television show Orphan Black, cloning is used as a scientific study on the behavioral adaptation of the clones.[102] In a similar vein, the book The Double by Nobel Prize winner Jos Saramago explores the emotional experience of a man who discovers that he is a clone.[103]

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Mom’s BMI may affect biological age of her baby Higher Body Mass Index (BMI) in a mother before pregnancy is associated with shorter telomere length a biomarker for biological age in her newborn. Her baby’s short telomere length means the baby’s cells have shorter lifespans.

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Two distinct cell types can initiate Crohn’s disease A new discovery could lead to personalized treatment for the debilitating gastrointestinal disorder called Crohn’s. There appear to be two distinct disease types. One expressed in normal colon tissue, the other in the small intestine. Detecting which type a patient has will assist her in her treatment and desire to get pregnant or carry a pregnancy.

Oct 14, 2016—–News ArchiveLatest research covered daily, archived weekly

Potential treatment of newborns via amniotic fluid? A breakthrough study offers promise for therapeutic management of congenital diseases in utero using designer gene sequences.

Oct 13, 2016—–News ArchiveLatest research covered daily, archived weekly

Infants use their prefrontal cortex to learn Researchers have always thought the prefrontal cortex (PFC) the brain region involved in some of the highest forms of cognition and reasoning was too underdeveloped in young children, especially infants, to participate in complex cognitive tasks. A new study suggests otherwise.

Oct 12, 2016—–News ArchiveLatest research covered daily, archived weekly

‘Amplifier’ helps make connections in the fetal brain A special amplifier makes neural signals stronger in babies then stops once neural connections are fully strengthened. Oct 11, 2016—–News ArchiveLatest research covered daily, archived weekly

Neurons migrate throughout infancy A previously unrecognized stage of brain development has just been recognized to continue long after birth. Neurons in the cerebral cortex, the outer layer of the brain, migrate into the cortex continuing growth throughout infancy.

Oct 10, 2016—–News ArchiveLatest research covered daily, archived weekly

Calcium triggers stem cells to generate bone Calcium is the main constituent of bone, and now is found to play a major role in regulating its growth. This new finding may affect treatment of conditions caused by too much collagen, such as fibrosis which thickens and scars connective tissue, as well in diseases of too little bone growth, such as Treacher Collins Syndrome (TCS).

Oct 7, 2016—–News ArchiveLatest research covered daily, archived weekly

How evolution has given us 5 fingers Have you ever wondered why our hands have exactly five fingers? Dr. Marie Kmita’s team has. The researchers at the Institut de recherches cliniques de Montral and Universit de Montral have uncovered a part of this mystery.

Oct 6, 2016—–News ArchiveLatest research covered daily, archived weekly New links between genes and bigger brains A number of new links between genes and brain size have been identified by United Kingdom scientists, hopefully opening up whole new avenues of understanding brain development including diseases like dementia.

Oct 5, 2016—–News ArchiveLatest research covered daily, archived weekly Progesterone in contraceptives promotes flu healing Over 100 million women are on hormonal contraceptives. All contain some form of progesterone, either alone or in combination with estrogen. Researchers found treatment with progesterone protects female mice against influenza by reducing inflammation and improving pulmonary function.

Oct 4, 2016—–News ArchiveLatest research covered daily, archived weekly

ZIKA in Men? “No procreation for 6 months” The Zika virus has largely spread via mosquitoes, but it can also be spread by sexual intercourse. Men who may have been exposed should wait at least six months before trying to conceive a child with a partner. Regardless whether they ever had any symptoms, say US federal health officials.

Oct 3, 2016—–News ArchiveLatest research covered daily, archived weekly Genetically modified baby boy – with 3 parents New, cheap and accurate DNA-editing techniques called CRISPR-Cas9 and SNT, or single nucleic targeting, are allowing for gene modification in humans. It is not science fiction anymore. In a first, a baby boy with modified DNA has been born in Mexico to overcome a mitochondrial disease that claimed the life of his two earlier sibblings

Sep 30, 2016—–News ArchiveLatest research covered daily, archived weekly Meet the world’s largest bony fish For the first time, the genome of the ocean sunfish (Mola mola), the world’s largest bony fish, has been sequenced. Researchers involved in the Genome 10K (G10K) project want to collect 10,000 nonmammalian vertebrate genomes for comparative analyses. The ocean sunfish genome has now revealed several altered genes that may explain its’ fast growth, large size and unusual shape.

Sep 29, 2016—–News ArchiveLatest research covered daily, archived weekly

Genetic variations that cause skull-fusion disorders During the first year of life, the human brain doubles in size, continuing to grow through adolescence. But sometimes, the loosely connected plates of a baby’s skull fuse too early, a disorder known as craniosynostosis. It can also produce facial and skull deformities, potentially damaging a young brain.

Sep 28, 2016—–News ArchiveLatest research covered daily, archived weekly

Heart defect genes both inside and outside the heart Congenital heart defects (CHDs) are a leading cause of birth defect-related deaths. How genetic alterations cause such defects is complicated by the fact that CHD’s many critical genes are unknown. Those that are known often contribute only small increases in CHD risk.

Sep 27, 2016—–News ArchiveLatest research covered daily, archived weekly Cesarean baby 15% more likely to become obese Cesarean born babies are 15% more likely to become obese as children than individuals born by vaginal birth and 64% more likely to be obese than their siblings born by vaginal birth. The increased risk may persist through adulthood. All of this data is according to a large study from Harvard T.H. Chan School of Public Health.

Sep 26, 2016—–News ArchiveLatest research covered daily, archived weekly

Male primes female for reproduction – but at a cost Research has discovered that male worms, through an invisible chemical “essence,” prime female worms for reproduction but with the unfortunate side effect of also hastening her aging. The results might lead to human therapies to delay puberty or prolong fertility.

Sep 23, 2016—–News ArchiveLatest research covered daily, archived weekly Why Tardigrades Are So Indestructible Tardigrades, or water bears, are microscopic animals capable of withstanding some of the most severe environmental conditions even being “dead” for 30 years, and then restored to life! Research from Japan has now created the most accurate picture yet of the tardigrade genome and why it matters to humans.

Sep 22, 2016—–News ArchiveLatest research covered daily, archived weekly Mouse bone marrow cells reduce miscarriage? Progenitor cells are like stem cells, but differentiated by a first step into one specific cell type. Research now finds the progenitor cells in bone marrow which replace worn out cells may help placental blood vessel growth and reduce abnormal placental development such as in pre-eclampsia.

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Stem Cell Therapy for Knees- Advanced Techniques

Posted: December 6, 2016 at 12:44 am

William Cimikoski, MD Medical Director of Utah Stem Cells, is a Medical Toxicologist that specializes in Stem Cell Joint Regeneration, Bioidentical Hormone Replacement Therapy, Medical Aesthetics, and Medial Weight Loss. With seven years of medical Residency and Fellowship specialty training, he is a foremost authority featured on HealthLine TV and ABCs Good 4 Utah.

Dr. Cimikoski was born and raised in Fairfield County, CT, in the suburbs of Manhattan. As a youth, he excelled in several contact sports, including hockey, lacrosse, and soccer. By the time he was 17-years-old he had suffered frequent sports related knee injuries (on both knees) and underwent numerous surgeries, ultimately culminating in major reconstructive knee surgery during his senior year in high school. This essentially ended his participation in competitive contact sports and he started to pursue his other passions in non-contact sports, including skiing and windsurfing. This is what brought him to the beautiful mountains of Utah where he could delight to his hearts content in the plentiful powdery snow.

He is a Medical Toxicologist who has completed seven years of specialty residency and fellowship training. He received his medical training at Brown University, where he did his Internship, followed by his Emergency Medicine Residency at Georgia Health Sciences University and Albany Medical Center. He also completed a Critical Care Fellowship in Medical Toxicology at Penn State University. To indulge his vice of windsurfing, he took a several year hiatus from the rat race and rigors of Emergency Medicine to work as a Ships Physician for Carnival Cruise Lines. While working for Carnival in 2004, he met his beautiful wife, Sarah (from Brazil), and they decided to settle in Utah in 2009 to start a family. They now have three young children under the age of five, two boys and a girl.

Dr. Cimikoski is keenly aware of the perils associated with osteoarthritis and orthopedic injuries, due to his own experiences and interest related to these debilitating processes. He is an exceptionally accomplished fitness and nutrition expert. This, coupled with his Medical Toxicology background, makes him uniquely qualified to provide the very best health care, and optimize his patients potential through the use of Bioidentical Hormones, Stem Cell Joint Regeneration, Medical Aesthetics, and Medical Weight Loss Management. He is pleased and eager to offer these cutting edge services with Utah Stem Cells, a new concept in medical healthcare wellness.

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2016 Scientific Program

Posted: December 4, 2016 at 2:44 pm

The 2016 Scientific Committee Sessions will be held Saturday, December 3, and Sunday, December 4. Each session will be offered twice. A question-and-answer period will occur at the end of each individual speaker presentation. Invited abstracts of these sessions will be published in the Program Book and on the flash drive containing the annual meeting abstracts.

All Scientific Program sessions will be recorded and made available through ASH On Demandafter the meeting.

Robert Brodsky, MD The Johns Hopkins University School of Medicine Baltimore, MD

Ross Levine, MD Memorial Sloan-Kettering Cancer Center New York, NY

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(Select) Ad Hoc Scientific Committee on Epigenetics and Genomics Joint Session: Scientific Committee on Blood Disorders in Childhood and Scientific Committee on Red Cell Biology Joint Session: Scientific Committee on Hematopoiesis and Scientific Committee on Myeloid Biology Scientific Committee on Bone Marrow Failure Scientific Committee on Hematopathology and Clinical Laboratory Hematology Scientific Committee on Hemostasis Scientific Committee on Immunology and Host Defense Scientific Committee on Iron and Heme Scientific Committee on Lymphoid Neoplasia Scientific Committee on Myeloid Neoplasia Scientific Committee on Plasma Cell Neoplasia Scientific Committee on Platelets Scientific Committee on Stem Cells and Regenerative Medicine Scientific Committee on Thrombosis and Vascular Biology Scientific Committee on Transfusion Medicine Scientific Committee on Transplantation Biology and Cellular Therapies

Enhancers and Chromatin Landscapes in Development and Cancer

Dr. Majeti will focus on chromatin accessibility patterns during normal humanhematopoiesis and AML evolution from pre-leukemic HSCs with a detailed discussion ofcohesin complex mutants.

Dr. Aifantis will focus on how higher order chromosomal structure is altered in leukemia and how key regulators of this process are involved in hematopoietic function and gene expression.

Dr. Ren will present data on state-of-the-art approaches to map human genomic architecture and how this process is altered during malignant transformation.

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AshAlizadeh,MD, PhD Stanford University Stanford,CA

BingRen,PhD University of San Diego La Jolla,CA Organization and Regulation of the Human Genome

IannisAifantis,PhD New York University New York,NY The Impact of 3D Chromosomal Topology in Acute Leukemia

RaviMajeti,MD, PhD Stanford University Stanford,CA Chromatin Accessibility Charts Human Hematopoiesis and Acute Myeloid Leukemia Evolution

Understanding and Repairing Faulty Red Blood Cells

Dr. Dean will focus on the biology of enhancers, gene regulatory elements that regulate transcription through long-range interactions with promoter regions and have highly tissue-specific functions, including in erythroid cells, as well as roles in promoting pathologic gene expression in disease states.

Dr. Lodish will present ongoing work focused on harnessing an integrative, mechanistic understanding of erythroid progenitor cell signaling pathways that control self-renewing cell divisions to envision novel therapies for anemias.

Dr. De Franceschi will describe the development of non-gene therapy strategies for clinical application, including approaches currently under clinical evaluation.

Dr. Cavazzana will present novel therapeutic approaches in an effort to cure the more prevalent inherited blood diseases worldwide. Results of ongoing clinical trials as well as of promising gene editing strategies will be summarized.

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ColleenDelaney,MD, MSc Fred Hutchinson Cancer Research Center Seattle,WA

Alex C.Minella,MD BloodCenter of Wisconsin Milwaukee,WI

AnnDean,PhD National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda,MD New Concepts in Genome Regulation

HarveyLodish,PhD Whitehead Institute for Biomedical Research Cambridge,MA PPARa Agonists and TGF Inhibitors Stimulate Red Blood Cell Production by Enhancing Self-Renewal of BFU-E Erythroid Progenitors

LuciaDe Franceschi,MD University of Verona Verona,Italy New Therapeutic Options: Alternates to Gene Therapy for Treating Hemoglobinopathies

MarinaCavazzana,MD, PhD Hpital Necker Enfants Malades Paris,France Gene Therapy Studies in Hemoglobinopathies: Successes and Challenges

Clonal Development of Hematopoietic Stem Cell Specification and Differentiation at Single Cell Resolution

Dr. Dick will describe clonal evolution of human hematopoiesis at single cell resolution.

Dr. Gottgens will present single cell molecular profiling experiments that reveal new aspects of blood stem cell regulation and their perturbation by leukemic factors.

Dr. Rothenberg will present a systems biology level understanding of the transcription networks that control lymphoid cell fate decisions.

Dr. Schroeder will present his work using transcription factor reporters to track myeloid lineage fate determination, and the instructive role of niche and environmental factors.

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YiZheng,PhD Cincinnati Children’s Hospital Cincinnati,OH

H. LeightonGrimes,PhD Cincinnati Children’s Hospital Cincinnati,OH

John E.Dick,PhD University Health Network Toronto,ON,Canada Molecular Events Defining Human Clonal Hematopoiesis at Single Cell Resolution

BertieGottgens,DPhil University of Cambridge Cambridge,United Kingdom Defining Cellular States, Differentiation Trajectories, and Regulatory Networks Through Single Cell Profiling

EllenRothenberg,PhD California Institute of Technology Pasadena,CA Transcription Factor Gene Fluorescent Reporters Track Lineage Fate in Lymphoid Commitment

TimmSchroeder,PhD ETH Zurich Basel,Switzerland Long-term Live Single Cell Quantification of Transcription Factor Dynamics

Ribosomes and Ribosomopathies

Dr. Barna will introduce the concept that not all ribosomes are created equal, and that translation by specialized ribosomes represents a separate layer of gene regulation that determines which mRNAs are effectively translated. Her work provides insights into how mutations in different ribosome proteins lead to a diverse spectrum of clinical features.*Please note that Dr. Barna will only be speaking at the Saturday session.*

Dr. Warren will provide structural insights into the mechanism by which mutations that cause Schwachman-Diamond anemia affect ribosome assembly.

Dr. Zon will describe a zebrafish model of Diamond Blackfan Anemia, and how chemical suppressor screens may lead to the discovery of novel therapeutics to ameliorate clinical aspects of the syndrome.

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NancySpeck,PhD University of Pennsylvania Perelman School of Medicine Philadelphia,PA

MariaBarna,PhD Stanford University Stanford,CA Specialized Ribosomes: A New Frontier in Gene Regulation, Organismal Biology, & Evolution

Alan J.Warren,MD, PhD University of Cambridge Cambridge,United Kingdom Shwachman-Diamond Syndrome and the Quality Control of Ribosome Assembly

Leonard I.Zon,MD Harvard Medical School, Boston Childrens Hospital Cambridge,MA Modeling Diamond Blackfan Anemia and Developing Therapeutics

Minimal Residual Disease in Hematology: Why, When, and How?

Dr. Wood will describe the key immunophenotypic principles that underlie minimal residual disease detection by flow cytometry and illustrate their application and clinical significance to the monitoring of acute leukemia.

Dr. Valk will discuss minimal residual disease detection in acute myeloid leukemia by means of polymerase chain reaction approaches using the multitude of available molecular markers in the context of clonal hematopoiesis.

Dr. Druley will focus on current strategies for using RNA sequencing as a modality for minimal residual disease detection. As we now move into the era of single-cell transcriptomes and error-corrected sequencing, we may move beyond simple quantitation of chromosomal rearrangements to identify also allele- and transcript-specific profiles of cancer cells as a tool for diagnostics, therapy and mechanistic understanding.

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TorstenHaferlach,MD MLL Munich Leukemia Laboratory Munich,Germany

BrentWood,MD, PhD Seattle Cancer Care Alliance Seattle,WA Multiparameter Flow Cytometry as a Powerful Tool

PeterValk,PhD Erasmus University Medical Center Rotterdam,Netherlands Molecular Minimal Residual Disease Detection in Acute Myeloid Leukemia

Todd E.Druley,MD, PhD Washington University School of Medicine in St. Louis St. Louis,MO Novel Technologies to Detect Minimal Residual Disease

Emerging Therapeutics to Alter Hemostasis and Thrombosis

Dr. Lenting will describe studies of the molecular interactions between factor VIII and von Willebrand factor. Detailed understanding of these interactions has recently been uncovered and can be used for development of improved long-acting factor VIII replacement therapies for treatment of hemophilia A.

Dr. Arruda will describe the discovery and biochemical characterization of factor IX Padua and translational studies. This form of factor IX has enhanced procoagulant activity and is being advanced into gene therapy trials for treatment of hemophilia B.

Dr. Coughlin will describe the discovery and characterization of protease-activated receptors (PARs). The work explained how the coagulation protease thrombin activates platelets and other cells and led to the development of the platelet inhibitory drug, vorapaxar. A crystal structure of a PAR-vorapaxar complex has helped to explain properties of the drug.

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AlanMast,MD, PhD BloodCenter of Wisconsin Milwaukee,WI

Peter JLenting,PhD French Institute of Health and Medical Research (INSERM) Le Kremlin-Bictre,France Von Willebrand Factor Interaction with FVIII: Development of Long Acting FVIII Therapies

ValderArruda,MD, PhD The Children’s Hospital of Philadelphia, University of Pennsylvania Philadelphia,PA Factor IX Padua: From Biochemistry to Gene Therapy

ShaunCoughlin,MD, PhD University of California San Francisco San Francisco,CA PAR1 Antagonists Development and Clinical Utility

Innate Immunity: The Green Light to Adaptive Responses

Dr. Trinchieri will discuss the role of inflammation, innate resistance and commensal microbiota in carcinogenesis, cancer progression and cancer therapy.

Dr. Gajewski will discuss innate immune sensing of cancer via the host Stimulator of INterferon Genes (STING) pathway and how this presents therapeutic opportunities to activate effective anti-tumor immunity.

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StanleyRiddell,MD Fred Hutchinson Cancer Research Center Seattle,WA

GiorgioTrinchieri,MD National Cancer Institute, National Institutes of Health Bethesda, Innate Immune Signaling in Regulation of Immunity

ThomasGajewski,MD, PhD University of Chicago Medical Center Chicago,IL Innate Immune Sensing in Anti-Tumor Immunity and Cancer Immunotherapy

From Iron Trafficking to Iron Traffic Jam

Dr. Carlomagno will discuss recent findings on the importance of ferritinophagy to maintain iron homeostasis in vivo. She will also present new data on the role of iron in regulating cell cycle progression and genome stability

Dr. Lakhal-Littleton will discuss the studies in tissue-specific and global hepcidin/ferroportin gene knockouts;offering insight into the interplay between cellular and systemic mechanisms in the regulation of iron levels in the heart and in its healthy functioning. Her studies raise the possibility that the hepcidin/ferroportin axis may also be important in other hepcidin and ferroportin-expressing tissues such as the kidney, the brain and the placenta.

Dr. Knutson will present recent insights from studies of knockout mouse models that aim to identify how various cells and organs, including the heart, take up non-transferrin-bound iron.

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Maria DomenicaCappellini,MD University of Milan – Fondazione iRCCS Ca’ Granda Ospedale Policlinico Milan Milan,Italy

FrancescaCarlomagno,MD, PhD Federico II University of Naples Naples,Italy Ferritinophagy and Cell Cycle Control

SamiraLakhal-Littleton,DPhil University of Oxford Oxford,United Kingdom Ferroportin Mediated Control of Iron Metabolism and Disease

MitchellKnutson,PhD University of Florida Gainesville,FL Non-Transferrin-Mediated Iron Delivery

Emerging Biology Leading to New Therapies in Follicular Lymphoma

Dr. Pasqualucci will introduce general concepts about the cell of origin in follicular lymphoma and the mechanisms associated with clonal evolution. She will then examine the genetic events that take place early in the history of the tumor clone and focus on the role of histone/chromatin modifier genes, including the methyltransferase KMT2D and the acetyltransferases CREBBP/EP300, in the stepwise progression of the disease from a subclinical state to a pathological entity.

Dr. Fitzgibbon will provide an introduction to genomic discovery in follicular lymphoma. He will review the next generation sequencing tools that are being used to identify genetic predisposition factors and to perform molecular profiling to identify signaling mutations that may be targeted therapeutically and which provide insights into disease prognosis.

Dr. Smith will focus her discussion on emerging new treatment approaches for follicular lymphoma based on the novel concepts and new targets described by Drs. Nadel and Fitzgibbon. She will focus on the disease heterogeneity and prognosis, the clinical unmet needs, and how clinical integration of the new molecular tools is leading to an evolution in the therapeutic regimens for patients with follicular lymphoma.

Please click here to review this session.

WendyStock,MD The University of Chicago Chicago,IL

LauraPasqualucci,MD Columbia University New York City,NY Genetic-Driven Disruption of Epigenetic Circuits As Early Steps In The Pathogenesis Of Follicular Lymphoma

JudeFitzgibbon,PhD Queen Mary University of London London,United Kingdom Genomic Discovery, Prognosis, and Target Therapy Development

Sonali M.Smith,MD The University of Chicago Medicine Chicago,IL Follicular Lymphoma Therapy Based on Biological Insights and Novel Concepts

Focusing on Myeloid Neoplasia Through Splicing

Dr. Krainer will update the audience on the spliceosoma complex and splicing machinery. He will discuss functional implications in normal and pathological conditions.

Dr. Halene will focus on the pathogenetic mechanisms underlying specific mutations in MDS.

Dr. Walter will discuss the clinical implications of spliceosome gene mutations in MDS, their distribution in diverse subgroups and their prognostic significance. He will explore novel therapeutic approachesbased on use of drugs that modulate splicing to treat spliceosome mutant MDS.

Please click here to review this session.

CristinaMecucci,MD, PhD University of Perugia Perugia,Italy

AdrianKrainer,PhD Cold Spring Harbor Laboratory Cold Spring Harbor,NY Spliceosome: Physiology and Disease Pathogenesis

StephanieHalene,MD, PhD Yale University School of Medicine New Haven,CT Functional Consequences of Spliceosome Mutations

Matthew J.Walter,MD Washington University in St. Louis St. Louis,MO Clinical Implications of Spliceosome Mutations: Epidemiology, Clonal Hematopoiesis, and Potential Therapeutic Strategies

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2016 Scientific Program

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From Stem Cells to Human Development – September 2016 …

Posted: at 2:42 pm

Organisers: Olivier Pourqui, Benoit Bruneau, Gordon Keller and Austin Smith

Date: 25th 28th September 2016

Location: Southbridge Hotel & Conference Center, Massachusetts, USA

Our understanding of human embryonic development is limited by the experimental inaccessibility of the system. Thus, we have been forced to make assumptions about how humans develop based on our knowledge of other mammals, especially the mouse. However, the recent explosion in stem cell research, particularly the generation of human pluripotent stem cells and the development of organoid culture systems, has provided new opportunities for investigating lineage choice, cell differentiation, tissue organisation and even organ morphogenesis using human cells. Such work promises not only to provide a more complete knowledge of our own developmental origins, but also to inform our efforts to understand and treat developmental disorders and, perhaps most importantly, to help bring regenerative therapies to the clinic.

Following on from our highly successful inaugural meeting in 2014, the second in this series of meetings From Stem Cells to Human Development brings together scientists with a common interest in understanding human development using stem cell systems. Topics to be discussed will include the regulation of pluripotency and differentiation, development of the major lineages and tissue morphogenesis, as well as translational aspects of human stem cell research.

The fees include;

It is expected that all attendees will stay for the duration of the Meeting.

A limited number of day delegate places are available, please email meetings@biologists.com for more information.

Southbridge Hotel & Conference Center is located in the USA, minutes from Sturbridge and less than an hours drive from Boston, Springfield, Hartford, CT, and Providence, RI. The building was originally constructed as an optical factory and has been refurnished and remodelled into a superb conference centre.

Southbridge Hotel & Conference Center 14 Mechanic Street Southbridge MA 01550 USA Tel: +1 508 765 8000

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Utah Stem Cells – Sports Medicine – 7430 Creek Rd, Sandy …

Posted: December 3, 2016 at 7:46 am

Specialties

We specialize in Stem Cell Joint Pain Treatment, Bioidentical Hormones for men and women, Stem Cell Aesthetics and Medical Weight Loss.

Established in 2015.

Utah Stem Cells was founded for the purpose of developing a new and exciting concept in a medical wellness center. Utilizing the latest advancements in stem cell technology, all of our services are specifically designed to enhance the quality of your life. We focus entirely on treatments that will help you feel stronger, with pain free joints, better mood, and a more beautiful appearance. You will look great and feel even better.

Dr. Bill Cimikoski, Medical Director of Utah Stem Cells, is a Medical Toxicologist that specializes in Stem Cell Joint Regeneration-a foremost authority featured on HealthLine TV and ABC’s Good 4 Utah. Assisted by experienced and trained nurses and physician assistants, Dr Bill offers the treatments that can benefit you the most, while making sure that from a toxicology perspective won’t hurt in the long term.

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Houndstongue | Montana Weed Control Association

Posted: at 7:44 am

(Cynoglossum officinale) Common Names

Gypsy flower, rats and mice, dog bur, beggers lice

Houndstongue is a biennial forb that forms a deep tap root and basal rosette the first year. It forms a flowering stem in its second year. The rosette leaves are broad, oblong, petioled and resemble a dogs tongue in shape. Leaves are alternate, up to one foot in length and up to three inches wide. They have smooth margins and are soft and velvety to touch. In the second year, stems form and often branch at the top of the plant. Plants can grow up to four feet in height. Flowers are five petaled, reddish-purple in color and produce four triangular, rounded seeds. They typically bloom in June and July. Seeds are small brown nutlets about 1/3 inch in length that easily attach to animals, vehicles, and humans. The entire plant has soft white hairs on it. The single tap root of houndstongue is thick, black and woody. Houndstoungue reproduces from seed only and each plant can produce up to 2,000 seeds. The plant dies after its second year.

The soft white hairs covering the plant, the basal leaves that resemble a hounds tongue, and the little brown burrs that stick to everything.

Houndstongue prefers well drained, relatively sandy and gravelly soils. It can also be found in shady areas and especially under the canopy of forests and wetter grasslands. It can be found in pastures and meadows, along roadsides and in disturbed sites.

Houndstongue carries an alkaloid poison that can kill livestock through loss of production of liver cells. Animals wont normally graze on it, but if cured in hay, it will remain toxic. Sheep are more resistant to this plant than cattle and horses. Horses are especially susceptible and symptoms of houndstongue ingestion include loss of weight, diarrhea, convulsions and even coma. As with many invaders, houndstongue does have medicinal properties as well and has been used as a remedy to acne, corn callus, eczema, and as a fever remedy.

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Photo credits:Photo Credits: Nancy Chow; Matt Lavin; Photo by Richard Old, http://www.xidservices.com

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Houndstongue | Montana Weed Control Association

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stem cells – decodingscience.missouri.edu

Posted: December 1, 2016 at 11:45 pm

Scientists use placental cells in lab to study virusBy Phillip Sitter | MU Bond Life Sciences Center

Megan Sheridan, an MU grad student, removes the base solution from a demonstrated sample of stem cells that will be grown into placental cells for study of Zika virus. Within four days of exposure to the correct hormones, the stem cells express genes of placental cells, and within another day start producing placental hormones. The cells are infected with Zika at day four to ensure maximum measurable interaction, as the stem cells naturally die in culture after about ten days. | photo by Phillip Sitter, Bond LSC

Scientists believe they have a better way to study how Zika virus can spread from a pregnant mother to her fetus and their technique doesnt even involve observations of babies in the womb or post-natal examinations.

As soon as we heard about Zika, everybodys light bulbs turned on, said Megan Sheridan, a graduate student at the University of Missouri Bond Life Sciences Center.

Sheridan works in the lab of Toshihiko Ezashi at Bond LSC, and she, in turn, is part of a cross-campus team researching Zika with R. Michael Roberts, Alexander Franz, Danny Schust and Ezashi.

Roberts lab studies pluripotent stem cells progenitor cells which can develop into any other type of cell in the body.

We use the proper signals to drive stem cells to become like placental cells, Sheridan explained. With this capability to stimulate stem cells with growth hormones and inhibitors at opportune moments, Roberts researchers realized they could create enough placental cells to create an environment similar to that of a womb in very early stages of pregnancy.

Megan Sheridan sits in front of a demonstration of her work with pluripotent stem cells. Sheridan is a graduate student who works in Toshihiko Ezashis lab, where she produces cells with placental characteristics from the stem cells in order to study placenta interaction with Zika virus. | photo by Phillip Sitter, Bond LSC

This is something which Sheridan thinks hasnt been done before in regards to studying placental interaction with Zika. Their technique could give a look into the first trimester, when epidemiological studies say a fetus is most susceptible to infection.

Roberts lab is trying to understand the placental barriers vulnerability to Zika virus in its early stage of pregnancy. During this time, an infection could occur even before the mother is aware she is pregnant.

If the lab uses their technique to understand how Zika virus enters placental cells, then potentially they could also learn how to strengthen the placenta as a barrier to Zika and make it a first line of defense against infection of the fetus in the womb. If developing babies dont get infected with Zika, then they wont suffer the consequences of birth defects.

One such defect is microcephaly where a baby is born with a smaller than expected head, which may in turn be a sign that their brain has not fully developed. While infection with Zika virus is rarely fatal or otherwise severe in itself many people dont even develop symptoms birth defects like microcephaly could cause further developmental problems like delays in learning how to speak and walk, intellectual disabilities, difficulty swallowing and problems with hearing and vision, according to global health organizations.

Microcephaly only became a widely documented effect of Zika after a particular strain surged across South and Central America with the infected mosquitoes that carry it, Sheridan explained, but this may be in part because previous Zika infections and outbreaks were themselves poorly documented.

While birth defects caused by Zika have drawn much media attention as the disease has spread northward through our hemisphere from Brazil, studies focusing on infection in the womb have only used placental material that has come to term. This may not be the most accurate way to see how the placenta gets infected in the first place early in pregnancy.

The pathway of Zika virus infection in lab mice isnt really comparable to human infection, because mice arent infected with this virus naturally. Only lab mice that have had their genomes altered to be able to acquire the virus have susceptibility to the infection that can be modeled.

Roberts lab is currently working with the African strain of Zika and obtained strains from Southeast Asia and Central America recently. Theres about a 99 percent genetic similarity across strains, Sheridan said.

Zika virus was first discovered in Africa in Uganda in 1947, according to the Centers for Disease Control and Prevention. The first human case was documented in 1952, and subsequent outbreaks also occurred in Southeast Asia and the Pacific Islands. The Pan American Health Organization issued an alert about the confirmed arrival of the virus in Brazil in May 2015.

The lab has completed Zika infections of some of their stem cell-produced placental cells. Sheridan reassured that even though the lab works with live viruses, Zika is not airborne, and none of their work involves mosquitoes.

Roberts lab submitted one grant application earlier this year to the National Institutes of Health for funding for their research. While that application was denied, Sheridan said that they have a lot more preliminary data now and are hoping to submit a revised grant soon.

She said that their original work was highly scored, but the funding level is still low, meaning that obtaining funds for research into Zika virus is highly competitive nationally.

Legislation to fund more efforts into studying and preventing transmission of Zika virus is caught in congressional gridlock, according to The New York Times and other media outlets.

In the mean time, as the Roberts lab prepares its next grant application submission, Sheridan said of her efforts that she is working hard to make progress on the project as quickly as possible.

Please visit the CDCs dedicated page for more information on Zika virus including advice for travellers and pregnant women, description of symptoms and treatment, steps you can take to control mosquitoes and prevent other means of transmission of the virus and more background on the history and effects of the disease.

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Stem cell controversy – Wikipedia

Posted: at 11:44 pm

The stem cell controversy is the consideration of the ethics of research involving the development, use, and destruction of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves the human embryos. For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using, or destroying human embryos, thus are minimally, if at all, controversial. Many less controversial sources of acquiring stem cells include using cells from the umbilical cord, breast milk, and bone marrow, which are not pluripotent.

For many decades, stem cells have played an important role in medical research, beginning in 1868 when Ernst Haeckel first used the phrase to describe the fertilized egg which eventually gestates into an organism. The term was later used in 1886 by William Sedgwick to describe the parts of a plant that grow and regenerate. Further work by Alexander Maximow and Leroy Stevens introduced the concept that stem cells are pluripotent, i.e. able to become many types of different cell. This significant discovery led to the first human bone marrow transplant by E. Donnal Thomas in 1968, which although successful in saving lives, has generated much controversy since. This has included the many complications inherent in stem cell transplantation (almost 200 allogeneic marrow transplants were performed in humans, with no long-term successes before the first successful treatment was made), through to more modern problems, such as how many cells are sufficient for engraftment of various types of hematopoietic stem cell transplants, whether older patients should undergo transplant therapy, and the role of irradiation-based therapies in preparation for transplantation.

The discovery of adult stem cells led scientists to develop an interest in the role of embroynic stem cells, and in separate studies in 1981 Gail Martin and Martin Evans derived pluripotent stem cells from the embryos of mice for the first time. This paved the way for Mario Capecchi, Martin Evans, and Oliver Smithies to create the first knockout mouse, ushering in a whole new era of research on human disease.

In 1998, James Thomson and Jeffrey Jones derived the first human embryonic stem cells, with even greater potential for drug discovery and therapeutic transplantation. However, the use of the technique on human embryos led to more widespread controversy as criticism of the technique now began from the wider non-scientific public who debated the moral ethics of questions concerning research involving human embryonic cells.

Since pluripotent stem cells have the ability to differentiate into any type of cell, they are used in the development of medical treatments for a wide range of conditions. Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed due to their ability to repair extensive tissue damage.[1]

Great levels of success and potential have been realized from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. These can become any cell type of the body, excluding placental cells. This ability is called pluripotency. Only cells from an embryo at the morula stage or earlier are truly totipotent, meaning that they are able to form all cell types including placental cells. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become.

Many of the debates surrounding human embryonic stem cells concern issues such as what restrictions should be made on studies using these types of cells. At what point does one consider life to begin? Is it just to destroy an embryo cell if it has the potential to cure countless numbers of patients? Political leaders are debating how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged. Other recent discoveries may extinguish the need for embryonic stem cells.[2]

Much of the criticism has been a result of religious beliefs, and in the most high-profile case, Christian US President George W Bush signed an executive order banning the use of federal funding for any cell lines other than those already in existence, stating at the time, “My position on these issues is shaped by deeply held beliefs,” and “I also believe human life is a sacred gift from our creator.”[3] This ban was in part revoked by his successor Barack Obama, who stated “As a person of faith, I believe we are called to care for each other and work to ease human suffering. I believe we have been given the capacity and will to pursue this research and the humanity and conscience to do so responsibly.” [4]

Some stem cell researchers are working to develop techniques of isolating stem cells that are as potent as embryonic stem cells, but do not require a human embryo.

Foremost among these was the discovery in August 2006 that adult cells can be reprogrammed into a pluripotent state by the introduction of four specific transcription factors, resulting in induced pluripotent stem cells.[5] This major breakthrough won a Nobel Prize for the discoverers, Shinya Yamanaka and John Gurdon.[6]

In an alternative technique, researchers at Harvard University, led by Kevin Eggan and Savitri Marajh, have transferred the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.[7]

Researchers at Advanced Cell Technology, led by Robert Lanza and Travis Wahl, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[8] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),[9] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos. “These are the first human embryonic cell lines in existence that didn’t result from the destruction of an embryo.” Lanza is currently in discussions with the National Institutes of Health to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.[10]

Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when used correctly, “can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells”. The extraction of this fluid is not thought to harm the fetus in any way. He hopes “that these cells will provide a valuable resource for tissue repair and for engineered organs, as well”.[11]

The status of the human embryo and human embryonic stem cell research is a controversial issue, as with the present state of technology, the creation of a human embryonic stem cell line requires the destruction of a human embryo. Most of these embryos are discarded. Stem cell debates have motivated and reinvigorated the pro-life movement, whose members are concerned with the rights and status of the embryo as an early-aged human life. They believe that embryonic stem cell research instrumentalizes and violates the sanctity of life and is tantamount to murder.[12] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell. The view of those in favor is that these embryos would otherwise be discarded, and if used as stem cells, they can survive as a part of a living human being.

A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, an estimated at least 400,000 such embryos exist.[13] This has led some opponents of abortion, such as Senator Orrin Hatch, to support human embryonic stem cell research.[14] See also embryo donation.

Medical researchers widely report that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering. In the future, most medical researchers anticipate being able to use technologies derived from stem cell research to treat a variety of diseases and impairments. Spinal cord injuries and Parkinson’s disease are two examples that have been championed by high-profile media personalities (for instance, Christopher Reeve and Michael J. Fox, who have lived with these conditions, respectively). The anticipated medical benefits of stem cell research add urgency to the debates, which has been appealed to by proponents of embryonic stem cell research.

In August 2000, The U.S. National Institutes of Health’s Guidelines stated:

…research involving human pluripotent stem cells…promises new treatments and possible cures for many debilitating diseases and injuries, including Parkinson’s disease, diabetes, heart disease, multiple sclerosis, burns and spinal cord injuries. The NIH believes the potential medical benefits of human pluripotent stem cell technology are compelling and worthy of pursuit in accordance with appropriate ethical standards.[15]

In 2006, researchers at Advanced Cell Technology of Worcester, Massachusetts, succeeded in obtaining stem cells from mouse embryos without destroying the embryos.[16] If this technique and its reliability are improved, it would alleviate some of the ethical concerns related to embryonic stem cell research.

Another technique announced in 2007 may also defuse the longstanding debate and controversy. Research teams in the United States and Japan have developed a simple and cost-effective method of reprogramming human skin cells to function much like embryonic stem cells by introducing artificial viruses. While extracting and cloning stem cells is complex and extremely expensive, the newly discovered method of reprogramming cells is much cheaper. However, the technique may disrupt the DNA in the new stem cells, resulting in damaged and cancerous tissue. More research will be required before noncancerous stem cells can be created.[17][18][19][20]

Update article to include 2009/2010 current stem cell usages in clinical trials.[21][22] The planned treatment trials will focus on the effects of oral lithium on neurological function in people with chronic spinal cord injury and those who have received umbilical cord blood mononuclear cell transplants to the spinal cord. The interest in these two treatments derives from recent reports indicating that umbilical cord blood stem cells may be beneficial for spinal cord injury and that lithium may promote regeneration and recovery of function after spinal cord injury. Both lithium and umbilical cord blood are widely available therapies that have long been used to treat diseases in humans.

This argument often goes hand-in-hand with the utilitarian argument, and can be presented in several forms:

This is usually presented as a counter-argument to using adult stem cells as an alternative that does not involve embryonic destruction.

This argument is used by opponents of embryonic destruction, as well as researchers specializing in adult stem cell research.

Pro-life supporters often claim that the use of adult stem cells from sources such as umbilical cord blood has consistently produced more promising results than the use of embryonic stem cells.[30] Furthermore, adult stem cell research may be able to make greater advances if less money and resources were channeled into embryonic stem cell research.[31]

In the past, it has been a necessity to research embryonic stem cells and in doing so destroy them for research to progress.[32] As a result of the research done with both embryonic and adult stem cells, new techniques may make the necessity for embryonic cell research obsolete. Because many of the restrictions placed on stem cell research have been based on moral dilemmas surrounding the use of embryonic cells, there will likely be rapid advancement in the field as the techniques that created those issues are becoming less of a necessity.[33] Many funding and research restrictions on embryonic cell research will not impact research on IPSCs (induced pluripotent stem cells) allowing for a promising portion of the field of research to continue relatively unhindered by the ethical issues of embryonic research.[34]

Adult stem cells have provided many different therapies for illnesses such as Parkinson’s disease, leukemia, multiple sclerosis, lupus, sickle-cell anemia, and heart damage[35] (to date, embryonic stem cells have also been used in treatment),[36] Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors.[37] Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.

Austria, Denmark, France, Germany, and Ireland do not allow the production of embryonic stem cell lines,[38] but the creation of embryonic stem cell lines is permitted in Finland, Greece, the Netherlands, Sweden, and the United Kingdom.[38]

In 1973, Roe v. Wade legalized abortion in the United States. Five years later, the first successful human in vitro fertilization resulted in the birth of Louise Brown in England. These developments prompted the federal government to create regulations barring the use of federal funds for research that experimented on human embryos. In 1995, the NIH Human Embryo Research Panel advised the administration of President Bill Clinton to permit federal funding for research on embryos left over from in vitro fertility treatments and also recommended federal funding of research on embryos specifically created for experimentation. In response to the panel’s recommendations, the Clinton administration, citing moral and ethical concerns, declined to fund research on embryos created solely for research purposes,[39] but did agree to fund research on leftover embryos created by in vitro fertility treatments. At this point, the Congress intervened and passed the Dickey Amendment in 1995 (the final bill, which included the Dickey Amendment, was signed into law by Bill Clinton) which prohibited any federal funding for the Department of Health and Human Services be used for research that resulted in the destruction of an embryo regardless of the source of that embryo.

In 1998, privately funded research led to the breakthrough discovery of human embryonic stem cells (hESC). This prompted the Clinton administration to re-examine guidelines for federal funding of embryonic research. In 1999, the president’s National Bioethics Advisory Commission recommended that hESC harvested from embryos discarded after in vitro fertility treatments, but not from embryos created expressly for experimentation, be eligible for federal funding. Though embryo destruction had been inevitable in the process of harvesting hESC in the past (this is no longer the case[40][41][42][43]), the Clinton administration had decided that it would be permissible under the Dickey Amendment to fund hESC research as long as such research did not itself directly cause the destruction of an embryo. Therefore, HHS issued its proposed regulation concerning hESC funding in 2001. Enactment of the new guidelines was delayed by the incoming George W. Bush administration which decided to reconsider the issue.

President Bush announced, on August 9, 2001, that federal funds, for the first time, would be made available for hESC research on currently existing embryonic stem cell lines. President Bush authorized research on existing human embryonic stem cell lines, not on human embryos under a specific, unrealistic timeline in which the stem cell lines must have been developed. However, the Bush Administration chose not to permit taxpayer funding for research on hESC cell lines not currently in existence, thus limiting federal funding to research in which “the life-and-death decision has already been made”.[44] The Bush Administration’s guidelines differ from the Clinton Administration guidelines which did not distinguish between currently existing and not-yet-existing hESC. Both the Bush and Clinton guidelines agree that the federal government should not fund hESC research that directly destroys embryos.

Neither Congress nor any administration has ever prohibited private funding of embryonic research. Public and private funding of research on adult and cord blood stem cells is unrestricted.

In April 2004, 206 members of Congress signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported.

In May 2005, the House of Representatives voted 238194 to loosen the limitations on federally funded embryonic stem-cell researchby allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donorsdespite Bush’s promise to veto the bill if passed.[45] On July 29, 2005, Senate Majority Leader William H. Frist (R-TN), announced that he too favored loosening restrictions on federal funding of embryonic stem cell research.[46] On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill (the Stem Cell Research Enhancement Act) 6337, which would have made it legal for the federal government to spend federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures.[47] On July 19, 2006 President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.

In 2005 and 2007, Congressman Ron Paul introduced the Cures Can Be Found Act,[48] with 10 cosponsors. With an income tax credit, the bill favors research upon nonembryonic stem cells obtained from placentas, umbilical cord blood, amniotic fluid, humans after birth, or unborn human offspring who died of natural causes; the bill was referred to committee. Paul argued that hESC research is outside of federal jurisdiction either to ban or to subsidize.[49]

Bush vetoed another bill, the Stem Cell Research Enhancement Act of 2007,[50] which would have amended the Public Health Service Act to provide for human embryonic stem cell research. The bill passed the Senate on April 11 by a vote of 63-34, then passed the House on June 7 by a vote of 247176. President Bush vetoed the bill on July 19, 2007.[51]

On March 9, 2009, President Obama removed the restriction on federal funding for newer stem cell lines. [52] Two days after Obama removed the restriction, the president then signed the Omnibus Appropriations Act of 2009, which still contained the long-standing Dickey-Wicker provision which bans federal funding of “research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death;”[53] the Congressional provision effectively prevents federal funding being used to create new stem cell lines by many of the known methods. So, while scientists might not be free to create new lines with federal funding, President Obama’s policy allows the potential of applying for such funding into research involving the hundreds of existing stem cell lines as well as any further lines created using private funds or state-level funding. The ability to apply for federal funding for stem cell lines created in the private sector is a significant expansion of options over the limits imposed by President Bush, who restricted funding to the 21 viable stem cell lines that were created before he announced his decision in 2001.[54] The ethical concerns raised during Clinton’s time in office continue to restrict hESC research and dozens of stem cell lines have been excluded from funding, now by judgment of an administrative office rather than presidential or legislative discretion.[55]

In 2005, the NIH funded $607 million worth of stem cell research, of which $39 million was specifically used for hESC.[56]Sigrid Fry-Revere has argued that private organizations, not the federal government, should provide funding for stem-cell research, so that shifts in public opinion and government policy would not bring valuable scientific research to a grinding halt.[57]

In 2005, the State of California took out $3 billion in bond loans to fund embryonic stem cell research in that state.[58]

China has one of the most permissive human embryonic stem cell policies in the world. In the absence of a public controversy, human embryo stem cell research is supported by policies that allow the use of human embryos and therapeutic cloning.[59]

According to Rabbi Levi Yitzchak Halperin of the Institute for Science and Jewish Law in Jerusalem, embryonic stem cell research is permitted so long as it has not been implanted in the womb. Not only is it permitted, but research is encouraged, rather than wasting it.

However in order to remove all doubt [as to the permissibility of destroying it], it is preferable not to destroy the pre-embryo unless it will otherwise not be implanted in the woman who gave the eggs (either because there are many fertilized eggs, or because one of the parties refuses to go on with the procedurethe husband or wifeor for any other reason). Certainly it should not be implanted into another woman…. The best and worthiest solution is to use it for life-saving purposes, such as for the treatment of people that suffered trauma to their nervous system, etc.

Similarly, the sole Jewish majority state, Israel, permits research on embryonic stem cells.

The Catholic Church opposes human embryonic stem cell research calling it “an absolutely unacceptable act.” The Church supports research that involves stem cells from adult tissues and the umbilical cord, as it “involves no harm to human beings at any state of development.”[60]

The Southern Baptist Convention opposes human embryonic stem cell research on the grounds that “Bible teaches that human beings are made in the image and likeness of God (Gen. 1:27; 9:6) and protectable human life begins at fertilization.”[61] However, it supports adult stem cell research as it does “not require the destruction of embryos.”[61]

The United Methodist Church opposes human embryonic stem cell research, saying, “a human embryo, even at its earliest stages, commands our reverence.”[62] However, it supports adult stem cell research, stating that there are “few moral questions” raised by this issue.[62]

The Assemblies of God opposes human embryonic stem cell research, saying, it “perpetuates the evil of abortion and should be prohibited.”[63]

The religion of Islam favors the stance that scientific research and development in terms of stem cell research is allowed as long as it benefits society while using the least amount of harm to the subjects. “Stem cell research is one of the most controversial topics of our time period and has raised many religious and ethical questions regarding the research being done. With there being no true guidelines set forth in the Qur’an against the study of biomedical testing, Muslims have adopted any new studies as long as the studies do not contradict another teaching in the Qur’an. One of the teachings of the Qur’an states that Whosoever saves the life of one, it shall be if he saves the life of humankind (5:32), it is this teaching that makes stem cell research acceptable in the Muslim faith because of its promise of potential medical breakthrough.”[64]

The First Presidency of The Church of Jesus Christ of Latter-day Saints “has not taken a position regarding the use of embryonic stem cells for research purposes. The absence of a position should not be interpreted as support for or opposition to any other statement made by Church members, whether they are for or against embryonic stem cell research.[65]

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Cell therapy – Wikipedia

Posted: at 11:41 pm

Cell therapy (also called cellular therapy or cytotherapy) is therapy in which cellular material is injected into a patient;[1] this generally means intact, living cells. For example, T cells capable of fighting cancer cells via cell-mediated immunity may be injected in the course of immunotherapy.

Cell therapy originated in the nineteenth century when scientists experimented by injecting animal material in an attempt to prevent and treat illness.[2] Although such attempts produced no positive benefit, further research found in the mid twentieth century that human cells could be used to help prevent the human body rejecting transplanted organs, leading in time to successful bone marrow transplantation.[3]

Today two distinct categories of cell therapy are recognized.[1]

The first category is cell therapy in mainstream medicine. This is the subject of intense research and the basis of potential therapeutic benefit.[4] Such research can be controversial when it involves human embryonic material.

The second category is in alternative medicine, and perpetuates the practice of injecting animal materials in an attempt to cure disease. This practice, according to the American Cancer Society, is not backed by any medical evidence of effectiveness, and can have deadly consequences.[1]

Cell therapy can be defined as therapy in which cellular material is injected into a patient.[1]

There are two branches of cell therapy: one is legitimate and established, whereby human cells are transplanted from a donor to a patient; the other is dangerous alternative medicine, whereby injected animal cells are used to attempt to treat illness.[1]

The origins of cell therapy can perhaps be traced to the nineteenth century, when Charles-douard Brown-Squard (18171894) injected animal testicle extracts in an attempt to stop the effects of aging.[2] In 1931 Paul Niehans (18821971) who has been called the inventor of cell therapy attempted to cure a patient by injecting material from calf embryos.[1] Niehans claimed to have treated many people for cancer using this technique, though his claims have never been validated by research.[1]

In 1953 researchers found that laboratory animals could be helped not to reject organ transplants by pre-inoculating them with cells from donor animals; in 1968, in Minnesota, the first successful human bone marrow transplantation took place.[3]

Bone marrow transplants have been found to be effective, along with some other kinds of human cell therapy for example in treating damaged knee cartilage.[1] In recent times, cell therapy using human material has been recognized as an important field in the treatment of human disease.[4] The experimental field of Stem cell therapy has shown promise for new types of treatment.[1]

In mainstream medicine, cell therapy is supported by a distinct healthcare industry which sees strong prospects for future growth.[5][6]

In allogeneic cell therapy the donor is a different person to the recipient of the cells.[7] In pharmaceutical manufacturing, the allogenic methodology is promising because unmatched allogenic therapies can form the basis of “off the shelf” products.[8] There is research interest in attempting to develop such products to treat conditions including Crohn’s disease[9] and a variety of vascular conditions.[10]

Research into human embryonic stem cells is controversial, and regulation varies from country to country, with some countries banning it outright. Nevertheless, these cells are being investigated as the basis for a number of therapeutic applications, including possible treatments for diabetes[11] and Parkinson’s disease.[12]

Cell therapy is targeted at many clinical indications in multiple organs and by several modes of cell delivery. Accordingly, the specific mechanisms of action involved in the therapies are wide ranging. However, there are two main principles by which cells facilitate therapeutic action:

Neural stem cells (NSCs) are the subject of ongoing research for possible therapeutic applications, for example for treating a number of neurological disorders such as Parkinson’s disease and Huntington’s disease.[20]

MSCs are immunomodulatory, multipotent and fast proliferating and these unique capabilities mean they can be used for a wide range of treatments including immune-modulatory therapy, bone and cartilage regeneration, myocardium regeneration and the treatment of Hurler syndrome, a skeletal and neurological disorder.[21]

Researchers have demonstrated the use of MSCs for the treatment of osteogenesis imperfecta (OI). Horwitz et al. transplanted bone marrow (BM) cells from human leukocyte antigen (HLA)-identical siblings to patients suffering from OI. Results show that MSCs can develop into normal osteoblasts, leading to fast bone development and reduced fracture frequencies.[22] A more recent clinical trial showed that allogeneic fetal MSCs transplanted in utero in patients with severe OI can engraft and differentiate into bone in a human fetus.[23]

Besides bone and cartilage regeneration, cardiomyocyte regeneration with autologous BM MSCs has also been reported recently. Introduction of BM MSCs following myocardial infarction (MI) resulted in significant reduction of damaged regions and improvement in heart function. Clinical trials for treatment of acute MI with Prochymal by Osiris Therapeutics are underway. Also, a clinical trial revealed huge improvements in nerve conduction velocities in Hurlers Syndrome patients infused with BM MSCs from HLA-identical siblings.[24]

HSCs possess the ability to self-renew and differentiate into all types of blood cells, especially those involved in the human immune system. Thus, they can be used to treat blood and immune disorders. Since human bone marrow (BM) grafting was first published in 1957,[25] there have been significant advancements in HSCs therapy. Following that, syngeneic marrow infusion[26] and allogeneic marrow grafting[27] were performed successfully. HSCs therapy can also render its cure by reconstituting damaged blood-forming cells and restoring the immune system after high-dose chemotherapy to eliminate disease.[28]

There are three types of HSCT: syngeneic, autologous, and allogeneic transplants.[21] Syngeneic transplantations occur between identical twins. Autologous transplantations use the HSCs obtained directly from the patient and hence do not cause any complications of tissue incompatibility; whereas allogeneic transplantations involve the use of donor HSCs, either genetically related or unrelated to the recipient. To lower the risks of transplant, which include graft rejection and Graft-Versus-Host Disease (GVHD), allogeneic HSCT must satisfy compatibility at the HLA loci (i.e. genetic matching to reduce the immunogenicity of the transplant). Mismatch of HLA loci would result in treatment-related mortality and higher risk of acute GVHD.[29]

In addition to BM derived HSCs, the use of alternative sources such as umbilical cord blood (UCB) and peripheral blood stem cells (PBSCs) has been increasing. In comparison with BM derived HSCs recipients, PBSCs recipients afflicted with myeloid malignancies reported a faster engraftment and better overall survival.[30] However, this was at the expense of increased rate of GVHD.[31] Also, the use of UCB requires less stringent HLA loci matching, although the time of engraftment is longer and graft failure rate is higher.[32][33]

In alternative medicine, cell therapy is defined as the injection of non-human cellular animal material in an attempt to treat illness.[1]Quackwatch labels this as “senseless”, since “cells from the organs of one species cannot replace the cells from the organs of other species” and because a number of serious adverse effects have been reported.[34]

Of this alternative, animal-based form of cell therapy, the American Cancer Society say: “Available scientific evidence does not support claims that cell therapy is effective in treating cancer or any other disease. In may in fact be lethal …”.[1]

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