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Category Archives: Washington Stem Cells

Understanding Stem Cell Therapy in Parkinsons Disease …

Posted: September 10, 2019 at 7:46 pm

On April 29, 2018, the Washington Post published an article examining commercial stem cell clinics in the United States that market non-FDA approved treatments directly to the public for a variety of health issues, including arthritis, macular degeneration and of particular note to us, Parkinsons disease (PD).

A typical treatment at one of these clinics involves removing fat cells from the abdomen (some clinics remove bone marrow or blood for this procedure), treating the cells in various ways in order to isolate mesenchymal stem cells or stromal cells from the removed tissue, and finally injecting these cells back into the body. The cells are re-introduced into the body in different locations (into the bloodstream, cerebral spinal fluid, nose, eye, etc.) depending on which disease is being targeted. Such treatments are performed for a fee, sometimes a large one, and are not covered by insurance.

Commercial clinics do not as a rule publish their results in peer-reviewed journals to demonstrate to the scientific community that the treatments work. Rather, they usually rely on anecdotes from patients as proof of efficacy. Some clinics are tracking their results by measuring variables such as quality of life before or after the procedure. However, without comparing the patients to a similar group who does not receive the treatment, it is hard to know whether any improvement is due to placebo effect or to the treatment itself.

Safety data is also limited, although there have been some publicized lawsuits claiming that these treatments resulted in harm. Stem cell researchers in general question whether cells harvested in such a way contain sufficient amounts of adult-derived stem cells to be meaningful. It is also unclear how this type of procedure would target the stem cells to the correct location. If stem cells are introduced in the nose for example, it is unclear how they would find their way to the basal ganglia and make the correct connection in order to help a person with Parkinsons disease.

In order for the medical community to accept this type of treatment as safe and beneficial, it would need to be shown to work in a placebo-controlled clinical trial for which participants do not pay, are aware of the known risks and benefits, and are carefully monitored throughout the trial. In addition, the trial would need to track adverse events, as well as record and share the outcomes of trial participants as they compare to the group of patients receiving a placebo treatment. So far this has not happened. The FDA is in fact studying mesenchymal stem cells in the laboratory in order to determine the best way to use them to help people, but these studies have not yet led to approved treatments. Most recently, the FDA filed federal complaints against two clinics that are marketing stem cell products without regulatory approval.

Researchers are working on it. Stem cells, often derived from a patient with Parkinsons disease, are currently being studied extensively in the laboratory, both to further our understanding of the molecular mechanisms that cause cell death in PD, and also as a test environment for new medications. However, there are currently no stem cell treatments for Parkinsons disease that have been developed and tested to the point that we are sure that they help and do not cause harm. Researchers however, are furiously underway to develop such a treatment. The research is focused on deciphering the best source of stem cells to use, the best ways to turn the stem cells into dopaminergic neurons (the type of neurons that are depleted in Parkinsons disease) and the best ways to introduce the cells into the brain for maximal effect and minimal harm.

1. Embryonic stem cells (ESCs) Stem cells derived from a human embryo, typically at a very early developmental stage. Early embryos created by in vitro fertilization (IVF) and are not going to be used, are typically the source of these cells. (This is as opposed to fetal stem cells which are typically derived from an older embryo.)2. Adult derived stem cells (also called tissue-specific stem cells) Stem cells found among, and then isolated from, differentiated cells in an adult. The most well understood of these are hematopoietic stem cells found in adult blood and bone marrow, which have been used clinically for decades, mostly to treat blood cancers and other disorders of the blood and immune systems.3. Umbilical cord stem cells Hematopoietic stem cells are also found in umbilical cord blood retrieved after delivery. These too are used clinically to treat blood cancers and some rare genetic disorders4. Mesenchymal stem cells also known as stromal cells are present in many tissues such as bone, cartilage and fat. They remain poorly understood, but likely have regenerative potential. These are the cells that are harvested at the commercial stem cell clinics described above.5. Induced pluripotent stem cells (iPSCs) Stem cells created from adult skin or blood cells that have been reprogrammed to revert to an embryonic state.6. Human parthenogenetic stem cells Stem cells created from an unfertilized human ovum.

Four groups dedicated to using stem cell therapies to treat Parkinsons disease have formed an international consortium known as G Force PD. Each of the four centers is planning a clinical trial to start in the next 1-4 years. They differ on the source of stem cells that they will be using (ESCs vs iPSCs). All will be injecting the cells directly into the basal ganglia part of the brain where the ends of the dopamine producing neurons live. The Parkinsons community eagerly awaits the implementation of these trials.

When open for enrollment, should I consider participating in a stem cell trial?When faced with an illness like PD, you can at times feel that it is worthwhile to try anything that may lead to a cure. Its important to always make sure however, that youre dealing with trusted information, proven therapies, and clinical trials that have been properly vetted by the medical community.

What if you want to get involved? Participation in a clinical trial that is investigating the use of stem cell treatments for Parkinsons disease will allow you to be involved in bringing such treatments to fruition. It is incredibly important to note however, that clinical trials that are entered on, the NIH-managed directory of all clinical trials, are not vetted by the NIH, and commercial stem cell clinics we mentioned earlier can put their treatments on this site to recruit patients. Most people dont realize this, which led to put a new disclaimer on their site stating: The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.

Therefore, in order to use safely, focus on the trials conducted at academic medical centers in the United States. Once you have identified a trial that you might be interested in, talk it over with your doctor before committing to anything.

Be aware that a clinical trial utilizing stem cells will likely require the cells to be injected directly into the brain, which will inevitably be associated with a certain amount of risk. You will need to discuss details of this risk with your doctor and the trial organizers.

Does APDA fund any stem cell research?APDA is committed to funding research to further our understanding of PD and to bring new treatments to patients as quickly as possible. Recent funding of Dr. Xiabo Mao, at Johns Hopkins University School of Medicine in Baltimore, MD, allowed him to use iPSCs to model PD and test a potential new avenue of treatment.

Be cautious of any clinic promoting a treatment that has not been proven by the FDA to be safe and effective. There is some promise in the area of using stem cells as a possible treatment for PD, but much more research needs to be done before such a therapy will be approved for clinical use.

Do you have a question or issue that you would like Dr. Gilbert to explore? Suggest a Topic

Dr. Rebecca Gilbert

APDA Vice President and Chief Scientific Officer

Dr. Gilbert received her MD degree at Weill Medical College of Cornell University in New York and her PhD in Cell Biology and Genetics at the Weill Graduate School of Medical Sciences. She then pursued Neurology Residency training as well as Movement Disorders Fellowship training at Columbia Presbyterian Medical Center. Prior to coming to APDA, she was an Associate Professor of Neurology at NYU Langone Medical Center. In this role, she saw movement disorder patients, initiated and directed the NYU Movement Disorders Fellowship, participated in clinical trials and other research initiatives for PD and lectured widely on the disease.

View all posts by Dr. Rebecca Gilbert

DISCLAIMER: Any medical information disseminated via this blog is solely for the purpose of providing information to the audience, and is not intended as medical advice. Our healthcare professionals cannot recommend treatment or make diagnoses, but can respond to general questions. We encourage you to direct any specific questions to your personal healthcare providers.

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Understanding Stem Cell Therapy in Parkinsons Disease ...

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Stem Cells Washington D.C., D.C. Surgical Arts

Posted: March 24, 2019 at 10:48 pm

The restorative properties of stem cells:

Stem cells are unique because they drive the natural healing process throughout your life. Stem cells are different from other cells in the body because they regenerate and produce specialized cell types. They heal and restore skin, bones, cartilage, muscles, nerves and other tissues when injured.

As a result, amazing new medical treatments are being developed to treat a range of diseases contemporary medicine currently deems difficult or impossible to treat. Among them are:

While stem cells can be found in most tissues of the body, they are usually buried deep, are few in number and are similar in appearance to surrounding cells. With the discovery of stem cells in teeth, an accessible and available source of stem cells has been identified.

The tooth is natures safe for these valuable stem cells, and there is an abundance of these cells in baby teeth, wisdom teeth and permanent teeth. The stem cells contained within teeth are capable of replicating themselves and can be readily recovered at the time of a planned dental procedure. Living stem cells found within extracted teeth were routinely discarded every day, but now, with the knowledge from recent medical research, your Doctor provides you the opportunity to save these cells for future use in developing medical treatments for your family.

Aside from being the most convenient stem cells to access, dental stem cells have significant medical benefits in the development of new medical therapies. Using ones own stem cells for medical treatment means a much lower risk of rejection by the body and decreases the need for powerful drugs that weaken the immune system, both of which are negative but typical realities that come into play when tissues or cells from a donor are used to treat patients.

Further, the stem cells from teeth have been observed in research studies to be among the most powerful stem cells in the human body. Stem cells from teeth replicate at a faster rate and for a longer period of time than do stem cells harvested from other tissues of the body.

Stem cells in the human body age over time and their regenerative abilities slow down later in life. The earlier in life that your familys stem cells are secured, the more valuable they will be when they are needed most.

Accessible The stem cells contained within teeth are recovered at the time of a planned procedure: Extraction of wisdom teeth, baby teeth or other healthy permanent teeth.

Affordable when compared with other methods of acquiring and preserving life saving stem cells: Peripheral blood, Bone Marrow, Cord blood etc, recovering Stem Cells from teeth is the most affordable and least invasive.

Convenience the recovery of stem cells from teeth can be performed in the doctors office anytime when a healthy tooth is being extracted.

Ease of Use The recovery of stem cells from teeth does not add any additional time on to a planned procedure. Your doctor does not require any additional equipment or training.

Healthy dental pulp contains stem cells that are among the most powerful stem cells in the body and replicate at a faster rate and for a longer period of time than other types of stem cells.Stem cells from teeth show great promise for future regenerative medical treatments of neurodegenerative diseases, heart disease, diabetes, bone diseases and brain and nerve injuries.

Any extracted tooth with a healthy pulp contains stem cells. Wisdom teeth, baby teeth and other permanent teeth i.e. healthy teeth that are fractured and teeth recommended for extraction for orthodontic purposes are all candidates for stem cell recovery and cryopreservation.

Age does not seem to play a major factor. All extracted healthy teeth contain stem cells. The younger you are then the younger the cells and these may be more beneficial in future regenerative therapies.

Diseases of different severity or tissue defects of different size will undoubtedly require different amounts of stem cells to heal. Conceptually, the more teeth are banked, the greater the potential for sufficient stem cells to treat various diseases.

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Stem Cells Washington D.C., D.C. Surgical Arts

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SCIENCE – Stem Cell Therapy Washington

Posted: November 22, 2018 at 7:43 pm

This website is continuously being updated. Please keep checking in frequently!

Researching Stem Cells on your own can be very frustrating and overwhelming. The world of stem cell research is exploding and the number of publications is going into the 100 thousands. So we are trying to make it easier here for you.

NIH currently has over 6600 studies on stem cells.


Regenerative medicine is a field of medical research developing treatments to repair or re-grow specific tissue in the body.There is a rising body of studies that reveals the power of mesenchymal stem cells (MSCs). Stem cells are multipotent stromal cells that can differentiate into a variety of cell types, including: osteoblasts (bone cells),chondrocytes(cartilage cells),myocytes (muscle cells), adipocytes (fat cells), neural cells. liver cells, heart muscle cells and many more. This phenomenon has been documented in many specific cells and tissues in living animals and their counterparts growing in laboratory tissue culture. Most Human Tissue has a rapid turnover rate. It is the availability of stem cells that assists in this process of regeneration. However with advanced age, your stem cells also age and proliferate much slower. In order to rejuvenatethis process stem cell therapy becomes necessary.

Amniotic Membranes have been used in clinical practice for over a century. Mainly, it was used in surgery as a biological coating. The first reported treatment with the amniotic membrane was performed in 1910 by J. Devis for the closing of skin defects. Since at least 1974 we have know about the power of umbilical cord healing cells. The umbilical cord stem cell injections became more common since 2000 and we are now almost 20 years into the clinical application of these MSCs in humans. Umbilical cord stem cells were initially only used in treating patients with joint problems. It was soon discovered that they contain naturally developing anti-inflammatory agents that actually do much more than stimulation of tissue repair. There have been no reports of patient rejection recorded so far. It is estimated that more than 500,000 injections have been used on patients without any cases of rejection or serious adverse side effects.

Stem cells currently are derived from several sources: amniotic, umbilical cord stem cells and adult stem cells. Adult stem cells are undifferentiated multipotent cells, found throughout the body, usually derived from bone marrow or adipose tissue.Kitsap Stemcells only uses mesenchymal stem cells derived from umbilical cord tissue. No stem cells are ever obtained from embryonic or fetal sources!

Amniotic membrane and cord blood derived tissue matrix presents as an excellent collagen scaffold, presentingwith active Collagen Types I, II, III, IV, V, and VII together with fibronectin and laminin, natural hyaluronic acid, fibroblasts, growth factors, cytokines, exosomes, alpha2macroglobulin, miRNA, and a wide spectrum of growth factors.

Selected Articles:

Umbilical cord stem cell: an overview.

For the latest publications of MSC stem cell check here!

For the latest REVIEWS on MSC research check here!

More Articles Here

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SCIENCE - Stem Cell Therapy Washington

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CONDITIONS – Stem Cell Therapy Washington

Posted: November 1, 2018 at 11:48 am

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Are Stem Cells Safe?

{Stemii Press release Jan 2108} In November 2017, theFDApublished several guidance documents describing regulatory oversight and expectations for HCT/P products, including regenerative medicine products. These documents include the regulatory framework for the development and oversight of regenerative medicine products and are intended to improve the understanding of how these products are regulated.


10s of Thousands of procedures have been safely performed!

Serving Kitsap, Jefferson, Mason & Clallam counties, including Poulsbo, Bremerton, Silverdale, Bainbridge Island, Kingston,Port Orchard, Hansville, Keyport, Bangor, Port Gamble, Port Ludlow, Port Townsend, Port Angeles, Sequim, Chimacum, Gig Harbor, Belfair, Seattle, Tacoma, Olympia,


All statements, opinions and advice on this website are for educational information. They are not a substitute for proper medical diagnosis and care. Like all medical treatments and procedures, results may significantly vary and positive results may not always be achieved. Please refer to FDA regulations regarding regenerative medicine. Pleasecontact usso we may evaluate your specific case.

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CONDITIONS - Stem Cell Therapy Washington

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Washington, DC – Stem Cells Transplant Institute

Posted: July 13, 2018 at 12:44 pm

There are few areas of health research that are as exciting and that hold as much potential for human health and treating disease as stem cells. Washington has been at the very forefront of stem cell therapies development.

The University of Washington Institute for Stem Cell and Regenerative Medicine is committed to the ethical pursuit of basic research to unleash the enormous potential of stem cells and thereby develop therapies and cures. Results are amazing and many people from Washington and the United States are already enjoying the benefits of stem cells therapy. United States is still in clinical trial phase and only a few clinics all over the country are legally approved.

Residents from Sammamish, Snoqualmie, Cottage Lake, Mercer Island, Bothell East and Union Hill Novelty Hill, can access today legally approved therapies in Costa Rica.

Stem Cells Transplant Institute in Costa Rica is one of the worlds leading adult stem cell therapy and research centers. We want to bring our patients from Washington stem cell-based treatments as quickly as possible with the highest standards of quality.Apply here.

The Stem Cells Transplant Institute of Costa Rica specializes in the legal treatment of Multiple Sclerosis, Diabetes, Lupus, Osteoarthritis, Rheumatoid Arthritis, Critical limb isquemia, Erectile Dysfunction, Parkinson, Neuropathy, Cardiovascular Disease, Knee Injury, Chronic Obstructive pulmonary disease, Alzheimer and Myocardial infarction.Contact us.

We use autologous Stem Cells therapies, this mean that the cells are obtained from your own fat or bone marrow, which is a very safe procedure, that plus the fact that we have one of the highest healthcare systems in the world, makes to Costa Rica the destiny of your choice. Dont hesitate tocontact us

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Washington, DC - Stem Cells Transplant Institute

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Washington University Mouse Embryonic Stem Cell Core …

Posted: July 7, 2018 at 8:42 pm

This core assists investigators with the generation of manipulated murine ES cells used to make sophisticated mouse models of human diseases.

The Murine Embryonic Stem Cell Core has been created to help you make mutations in mouse embryonic stem cells. The core has several missions including: development of state-of-the art reagents for the production of targeted mutations in embryonic stem cells, the creation of quality-controlled embryonic stem cell lines, and the teaching of methods for embryonic stem cell culture and manipulation. The core provides seven different embryonic stem cell lines for the WUMS research community. In addition, this core provides a teaching service, so that hands-on production of targeted ES clones can be learned. Finally, the core will arrange additional services for your ES clones such as karyotyping, MAP testing, and blastocyst injections. By providing a comprehensive service, we hope to facilitate the production of gain-of-function and loss-of-function mouse models for our faculty.

Service available to Washington University and other non-profit organizations.

Priority service for All entities, including for-profit organizations.

Pricing is subject to core verification

Please refer to the core website under Services for detailed service costs.

AFFILIATIONSDepartments of MedicineDevelopmental BiologyCell Biology & Physiology

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Are Stem Cells the Next Frontier for diabetes treatment …

Posted: September 24, 2017 at 6:57 am

Charles A. Goldthwaite, Jr., Ph.D.

Diabetes is a devastating disease that affects millions of people worldwide. The major forms of the disease are type 1 and type 2 diabetes. In type 1 diabetes, the body's immune system aberrantly destroys the insulin-producing beta cells (b-cells) of the pancreas. Type 2 diabetes, the more common form, is characterized both by insulin resistance, a condition in which various tissues in the body no longer respond properly to insulin action, and by subsequent progressive decline in b-cell function to the point that the cells can no longer produce enough additional insulin to overcome the insulin resistance. Researchers are actively exploring cell replacement therapy as a potential strategy to treat type 1 diabetes, because patients with this disease have lost all or nearly all b-cell function. However, if a safe and cost-effective means for replenishing b-cells were developed, such a treatment strategy could also be useful for the larger population with type 2 diabetes. One of the major challenges of cell replacement therapy is the current insufficient supply of b-cells from human organ donors. This article focuses on stem cells as potential sources for deriving new b-cells.

According to the International Diabetes Federation, diabetes currently affects 7% of the world's population nearly 250 million individuals worldwide.1 This total is expected to rise to 380 million by 2025 as a result of aging populations, changing lifestyles, and a recent worldwide increase in obesity. Although projections for increases in diabetes prevalence suggest that the greatest percentage gains will occur in Asia and South America,2,3 all nations will experience a rising disease burden. According to the National Diabetes Fact Sheet, which was compiled using information from the Centers for.

According to the National Diabetes Fact Sheet, which was compiled using information from the Centers for Disease Control and Prevention and other Federal and non-Federal organizations, 20.8 million U.S. children and adults have diabetes (6.2 million of whom are currently undiagnosed).4 An estimated 54 million Americans have "pre-diabetes", a condition defined by blood glucose levels that are above normal but not sufficiently high to be diagnosed as diabetes. In 2005, 1.5 million new cases of diabetes were diagnosed in Americans aged 20 years or older.4 If present trends continue, 1 in 3 Americans (1 in 2 minorities) born in 2000 will develop diabetes in their lifetimes.5

Diabetes is currently the sixth leading cause of death in the U.S.4 It is associated with numerous health complications, including increased risk for heart disease, stroke, kidney disease, blindness, and amputations. In 2007, the total annual economic cost of diabetes was estimated to be $174 billion dollars.6 Direct medical expenditures account for the vast majority of this total ($116 billion), although lost productivity and other indirect costs approached nearly $58 billion. The American Diabetes Association estimates that one out of every 10 health care dollars currently spent in the U.S. is used for diabetes and its complications.6

While diabetes can be managed, at present it cannot be cured. As a result, it is a lifelong and often disabling disease that can severely impact the quality of life of those who are afflicted. Based on several recent discoveries, however, researchers have begun to ask if a new treatment approach is on the horizon can stem cells that are derived from adult or embryonic tissues generate new pancreatic b-cells to replace those that have failed or been destroyed? Cell replacement therapy is one of many research avenues being pursued as a potential treatment strategy for type 1 diabetes. The strategy may also have implications for ameliorating type 2 diabetes. One of the key obstacles to advancing such therapy is the current inadequate supply of cadaveric donor pancreata as a source of cells for transplantation. Additionally, it is not currently possible to induce a patient's own cells to regenerate new b-cells within the body. Thus, researchers are actively investigating potential sources of new beta cells, including different types of stem cells. This article will focus on the various types of stem cells that are candidates for use in pancreatic regeneration and will discuss the challenges of using such cells as therapy for diabetes.

Diabetes results from the body's inability to regulate the concentration of sugar (glucose) in the blood. Blood glucose concentration is modulated by insulin, a hormone produced by pancreatic b-cells and released into the bloodstream to maintain homeostasis. In healthy individuals, b-cells counteract sharp increases in blood glucose, such as those caused by a meal, by releasing an initial "spike" of insulin within a few minutes of the glucose challenge. This acute release is then followed by a more sustained release that may last for several hours, depending on the persistence of the elevated blood glucose concentration. The insulin release gradually tapers as the body's steady-state glucose concentration is reestablished. While postprandial insulin release is stimulated by factors other than blood glucose, the blood sugar concentration is the major driver. When the b-cells fail to produce enough insulin to meet regulatory needs, however, the blood glucose concentration rises. This elevated concentration imposes a metabolic burden on numerous body systems, dramatically increasing the risk of premature cardiovascular disease, stroke, and kidney failure. Moreover, the risk for certain diabetes-related complications increases even at blood glucose concentrations below the threshold for diagnosing diabetes.

At present, there is no cure for diabetes.b-cell failure is progressive7; once the condition is manifest, full function usually cannot be restored. Those with type 1 diabetes require daily insulin administration to survive. Persons with type 2 diabetes must control their elevated blood glucose levels through various means, including diet and exercise, oral antihyperglycemic (blood glucose-lowering) drugs, and/or daily insulin shots. Most people who live with type 2 diabetes for a period of time will eventually require insulin to survive.

As noted earlier, there are different forms of diabetes. Type 1 diabetes results when a person's immune system mistakenly attacks and destroys the b-cells. This type of diabetes was once referred to as "juvenile-onset diabetes," because it usually begins in childhood. Type 1 diabetes accounts for 510% of diabetes cases, and people with type 1 diabetes depend on daily insulin administration to survive.

By contrast, type 2 diabetes is a metabolic disorder that results from a decline in b-cell function combined with insulin resistance, or the inability to use insulin effectively in peripheral tissues such as the liver, muscles, and fat.8 Onset is associated with genetic factors and with obesity, and type 2 diabetes disproportionately affects certain minority groups. 3 Unlike type 1 diabetes, type 2 is largely preventable. Numerous studies have suggested that the environmental and behavioral factors that promote obesity (e.g., a sedentary lifestyle, a high-calorie diet) have profoundly influenced the recent rise in the prevalence of type 2 diabetes.9 This trend suggests that type 2 diabetes will continue to be a major health care issue.

There is great interest in developing strategies to expand the population of functional b-cells. Possible ways to achieve this include physically replacing the b-cell mass via transplantation, increasing b-cell replication, decreasing b-cell death, and deriving new b-cells from appropriate progenitor cells.10 In 1990, physicians at the Washington University Medical Center in St. Louis reported the first successful transplant of donor-supplied pancreatic islet tissue (which includes b-cells; see below) in humans with type 1 diabetes.11 By the end of the decade, many other transplants had been reported using various protocols, including the widely-known "Edmonton protocol" (named for the islet transplantation researchers at the University of Alberta in Edmonton).12-14 This protocol involves isolating islets from the cadaveric pancreatic tissue of multiple donors and infusing them into the recipient's portal vein. However, the lack of available appropriate donor tissue and the strenuous regimen of immunosuppresive drugs necessary to keep the body from rejecting the transplanted tissue limit the widespread use of this approach. Moreover, the isolation process for islets damages the transplantable tissue; as such, 23 donors are required to obtain the minimal b-cell mass sufficient for transplantation into a single recipient.13 While these strategies continue to be improved, islet function declines relatively rapidly post-transplant. For example, a long-term follow-up study of Edmonton transplant patients indicated that less than 10% of recipients remained insulin-independent five years after transplant.15

These challenges have led researchers to explore the use of stem cells a possible therapeutic option. Type 1 diabetes is an appropriate candidate disease for stem cell therapy, as the causative damage is localized to a particular cell type. In theory, stem cells that can differentiate into b-cells in response to molecular signals in the local pancreatic environment could be introduced into the body, where they would migrate to the damaged tissue and differentiate as necessary to maintain the appropriate b-cell mass. Alternately, methods could be developed to coax stem cells grown in the laboratory to differentiate into insulin-producing b-cells. Once isolated from other cells, these differentiated cells could be transplanted into a patient. As such, stem cell therapy would directly benefit persons with type 1 diabetes by replenishing b-cells that are destroyed by autoimmune processes, although it would still be necessary to mitigate the autoimmune destruction of b-cells. The strategy would also benefit those with type 2 diabetes to a lesser extent by replacing failing b-cells, although the insulin resistance in peripheral tissues would remain present. As discussed in the following sections, however, debate continues about potential source(s) of pancreatic stem cells.

Figure 7.1.The pancreas is located in the abdomen, adjacent to the duodenum (the first portion of the small intestine). A cross-section of the pancreas shows the islet of Langerhans which is the functional unit of the endocrine pancreas. Encircled is the beta cell that synthesizes and secretes insulin. Beta cells are located adjacent to blood vessels and can easily respond to changes in blood glucose concentration by adjusting insulin production. Insulin facilitates uptake of glucose, the main fuel source, into cells of tissues such as muscle.

2001 Terese Winslow, Lydla Kibluk

The pancreas is a complex organ made up of many cell types. The majority of its mass is comprised of exocrine tissue, which contains acinar cells that secrete pancreatic enzymes into the intestine to aid in food digestion. Dispersed throughout this tissue are thousands of islets of Langerhans, clusters of endocrine cells that produce and secrete hormones into the blood to maintain homeostasis. The insulin-producing b-cell is one type of endocrine cell in the islet; other types include alpha cells (a-cells), which produce glucagon, gamma cells (g-cells), which produce pancreatic polypeptide, and delta cells (d-cells), which produce somatostatin.

Each of these cell types arises from a precursor cell type during the process of development. Therefore, the key step for using stem cells to treat diabetes is to identify the precursor cell(s) that ultimately give rise to the b-cell. However, generating these cells is more complex than simply isolating a hypothetical "pancreatic stem cell." Experiments have indicated that embryonic and adult stem cells can serve as sources of insulin-secreting cells,16 leading researchers to explore several avenues through which stem cells could feasibly be used to regenerate b-cells. However, many challenges must be addressed before a particular cell type will become established for this approach.

The human body has inherent mechanisms to repair damaged tissue, and these mechanisms remain active throughout life. Thus, there is reason to speculate that the adult pancreas may be aided by some type of regenerative system that replaces worn-out cells and repairs damaged tissue in response to injury. Such a system could theoretically be supported by precursor or stem cells, located in the endocrine pancreas or elsewhere, which could be coaxed to differentiate in response to select molecular or chemical stimuli. But do these cells exist? If so, how can they be recognized, isolated, and cultured for therapeutic use? How quickly could they produce sufficient numbers of b-cells to offset damage caused by diabetes processes? Alternately, what if cells that have the capability to regenerate b-cells exist in the body but are committed to differentiate into some other cell type? Could embryonic stem (ES) cell lines, which have the potential to develop into cells from all lineages, then be derived in vitro and be directed to differentiate into b-cells? These questions will be explored in the following sections, which review the types of candidate stem cells for diabetes.

Whether b-cell progenitors are present in the adult pancreas is a controversial topic in diabetes research. Several recent studies in rodents have indicated that the adult pancreas contains some type of endocrine progenitor cells that can differentiate toward b-cells.16 However, researchers have not reached consensus about the origin of the bona fide pancreatic stem cell (if it exists) or the mechanism(s) by which b-cells are regenerated.17 For example, a pivotal study by Dor and colleagues used genetic lineage tracing in adult mice to determine how stem cells contribute to the development of b-cells.18 Their analysis indicated that new b-cells arise from pre-existing ones, rather than from pluripotent stem cells, in adult mice. As such, the authors noted that b-cells can proliferate in vivo, thereby "cast[ing] doubt on the idea that adult stem cells have a significant role in beta-cell replenishment." Soon after this report was published, Seaberg and coworkers reported the identification of multipotent precursor cells from the adult mouse pancreas.19 These novel cells proliferated in vitro to form colonies that could differentiate into pancreatic -, b-, and -cells as well as exocrine cells, neurons, and glial cells. Moreover, the beta-like cells demonstrated glucose-dependent insulin release, suggesting possible therapeutic application to diabetes. Several subsequent studies have also reported the existence of pancreatic stem/precursor cells in vitro or in vivo.20-22 One recent report suggests that such cells exist in the pancreatic ductal lining and can be activated autonomously in response to injury, increasing the b-cell mass through differentiation and proliferation.23

The study of pancreatic regeneration continues to evolve, and many claims have been made regarding cells believed to be involved in the process. In the last decade, reports have described various putative pancreatic stem cells embedded in the pancreatic islets,24,25 pancreatic ducts,23,26 among the exocrine acinar cells,20,21 and in unspecified pancreatic locales19,27 in rodent models, as well as from human adult pancreatic cell lines,28 islet tissue,29 and non-islet tissues discarded after islets have been removed for transplantation.30-32 These cells are identified by the presence of one or more cell-surface proteins, or markers, known to be associated with a particular stem cell lineage. However, these studies illustrate several challenges shared by all researchers who seek to identify the "pancreatic stem cell". First, all potential stem cell candidates identified to date are relatively rare; for instance, the precursor cells identified by Seaberg are present at the rate of 1 cell per 3,0009,000 pancreaccells.19 Because there are so few of these putative stem cells, they can be difficult to identify. Additionally, the choice of marker can select for certain stem cell populations while possibly excluding others. Interestingly, the progenitor cells identified in the Seaberg study lacked some known b-cell markers such as HNF3b, yet they were able to generate b-cells. Thus, a hypothetical experiment that used only HNF3b as a marker for b-cell differentiation would likely not identify this stem cell population. Moreover, techniques used to study the pancreatic tissue, such as the genetic lineage technique of Dor, could possibly interfere with the generation of new b-cells from stem or precursor cells.33

As such, the possibility remains that b-cells could be regenerated by differentiation of endogenous stem cells, by proliferation of existing b-cells, or a combination of the two mechanisms.

Further research to elucidate conditions under which b-cells can proliferate may help to develop new therapeutic approaches. For example, several advances have recently been made from studies of pregnancy and pregnancy-related diabetes (gestational diabetes) in mice. During pregnancy, pancreatic islet cells normally expand in number to meet increased metabolic demands. Researchers have found that the protein HNF4-alpha helps increase b-cell mass, and that pregnancy-related decreases in levels of another protein, menin, also enable b-cell proliferation.34,35 Insights may also arise from research on another organ, the liver. Unlike the pancreas, the liver has an inherently high capacity for regeneration. New strategies for inducing pancreatic islet cell growth may emerge from knowledge of how liver cells develop from progenitor cells during early development such that the resulting adult organ retains substantial regenerative capacity.36 In another research avenue, scientists are exploring whether it may be possible to redirect adult pancreatic cells in the body to change from their original cell type into b-cells.

Furthermore, various reports have also described putative stem cells in the liver, spleen, central nervous system, and bone marrow that can differentiate into insulin-producing cells.17 While it is possible that such pathways may exist, these results are currently under debate within the research community. In another research avenue, scientists recently reported that differentiated cells, including adult human skin cells, can be genetically "reprogrammed" to revert to a pluripotent state, resembling that of embryonic stem (ES) cells.37 The researchers refer to these cells as induced pluripotent stem (iPS) cells. Their method involved introducing a defined set of genes into the differentiated cells. This approach may facilitate the establishment of human iPS cell lines from patients with specific diseases that could be used as research tools. This technique, or variations of it, may also one day allow patient-specific stem cells to be generated for use in stem cell-based therapies. However, the genes used for reprogramming were introduced into the cells using a virus-based method, which could have adverse clinical effects. If, however, safe alternate methods based on this research can be developed for reprogramming cells, then iPS cells may lead to novel, personalized therapies.

The challenges associated with identifying and isolating adult "pancreatic stem cells" has led some researchers to explore the use of ES cells as a source of insulin-producing cells. Several factors make ES cells attractive for this application.33 First, given the complexity of pancreatic tissue, identified b-cell precursors would likely be difficult to isolate from the adult pancreas. If isolated, the cells would then need to be replicated ex vivo while keeping them directed toward a b-cell lineage. Second, protocols to grow and expand mature b-cells in culture have met with technical challenges. ES cells, which are pluripotent cell lines (they can give rise to all cell types of the embryo) that can be induced to develop into various lineages based on culture conditions, may therefore represent a future option for b-cell regeneration.

To date, several human ES cells lines have been successfully derived.38-40 While these cell lines serve as resources for exploring the mechanisms of development, their potential use in a clinical setting is limited by several factors, most notably ethical concerns and the risk of teratoma development. (For a more detailed discussion of the scientific challenges associated with clinical application of ES cells, see Chapter 6, "Mending a Broken Heart: Stem Cells and Cardiac Repair," p.59). In addition, researchers are only beginning to unlock the myriad factors that come into play as a once-pluripotent cell differentiates into a unipotent cell, one that can contribute to only one mature cell type.41 For example, several recent reports indicate that mouse42 and human43 ES cells can be successfully differentiated into endodermal cells, the precursors of pancreatic cells. In addition, insulin-producing cells have been derived from mouse44,45 and human46 ES cells.

However, it should be noted that directed differentiation of ES cells toward the b-cell has not been reported. Beta cells appear relatively late during embryonic development, suggesting that their presence involves the temporal control of a considerable number of genes. Moreover, the creation of patient-specific, stem cell-derived b-cells for transplantation requires genetic matching to lessen the immune response. Generating immune-matched tissues requires the therapeutic cloning of human ES cells, which has not been accomplished to date. A fraudulent claim to the contrary in 2005 by South Korean researcher Woo Suk Hwang47 ignited international controversy within the scientific community48 and illustrated the scientific and ethical challenges of using ES cells as a source of transplant tissue. Despite current gaps in knowledge, researchers recognize the potential of ES cells as sources of specialized cells such as the b-cell, and the study of ES cells provides insight into the processes that govern differentiation and specialization.

Clearly, using stem cells to treat diabetes will require additional knowledge, both in the laboratory and in the clinic. This section will suggest several envisioned approaches for stem-cell derived diabetes therapies and discuss key considerations that must be addressed for their successful application.

Contingent upon the development of appropriate protocols, stem cells could theoretically be used to treat diabetes through two approaches.49 Both strategies would require the isolation and in vitro expansion of a homogenous population of b-cell precursor cells from appropriate donor tissue. Once a population of these cells has been generated, they could either 1) be induced to differentiate into insulin-producing cells in vitro and then be transplanted into the diabetic patient's liver, or 2) be injected into the circulation along with stem cell stimulators, with the hope that the cells will "home in" to the injured islets and differentiate into a permanent self-renewing b-cell population.

Because type 1 diabetes is an autoimmune disease, controlling the autoimmune response is critical to the success of any potential stem cell-based therapy. Type 1 diabetes is characterized by the action of b-cell-specific, autoreactive T-cells. Even if the regenerative properties of the pancreas remain functional, the continued presence of these T-cells effectively counteracts any endogenous repair and would likely decimate populations of newly-regenerated or transplanted insulin-producing cells. However, the autoimmune response has been successfully averted in non-obese diabetic mice either by using anti-T-cell antibodies to eliminate the majority of the autoreactive cells50 or by transplanting bone marrow from a diabetes-resistant donor (with a sublethal dose of irradiation) into the diabetic animal.51-53 Both strategies appear to enable the replenishment of insulin-secreting cells and the eventual restoration of normal blood glucose levels, although the process requires weeks to months and may necessitate additional therapy. Other strategies being explored include altering the immune tolerance through the use of monoclonal antibodies,54 proteins,55 and oligonucleotides.56

Other clinical challenges, including safety, tracking of the stem cells, delivery of the cells to the targeted tissue within a clinically relevant time frame (for transplanted cells), identification of ways to promote long-term survival and functioning of regenerated b-cells, ease of obtaining the cells, and cost, parallel those encountered with all applications of stem cell-based regenerative therapy. These issues must be addressed once the "pancreatic stem cell" population has been identified conclusively. Given current debate on this issue, the routine clinical application of stem-cell based regenerative therapy for the treatment of diabetes remains a future goal, albeit one with great potential.

As an additional source of information, an extensive discussion of research challenges and strategies for achieving the goal of cell replacement therapy for Type 1 diabetes is presented in Advances and Emerging Opportunities in Type 1 Diabetes Research: A Strategic Plan, available on the NIH web site at

The results discussed in this article demonstrate the many challenges that must be addressed before stem cells can be used to regenerate islet tissue in persons with diabetes. Debate continues on the identification of the "pancreatic stem cell," and at present it is difficult to ascertain which cell type has the greatest potential for diabetes therapy. Moreover, modulating the autoimmune response in type 1 diabetes remains a significant challenge regardless of the type of cell that is transplanted, and it will also be important to address the insulin resistance in type 2 diabetes, as well as factors that contribute to obesity. However, diabetes is a disease with a major deficiency in the functioning of one type of cell, and there is potential of stem cells to treat type 1 diabetes and to improve the quality of life for those with type 2 diabetes. As researchers learn more about the mechanisms that govern stem cell programming, differentiation, and renewal, their ability to identify, isolate, and culture candidate stem cells will continue to improve. While stem cells can be currently considered a frontier for diabetes therapy, they may one day become its basis..

Chapter 6|Table of Contents|Chapter 8

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Revolutionary cancer treatment comes with hefty price tag – Washington Examiner

Posted: September 5, 2017 at 9:49 am

A new cancer treatment will be sold for nearly half a million dollars, sparking criticism from some patient advocates.

On Wednesday, the Food and Drug Administration approved the first gene therapy in the U.S. called Kymriah, which customize a patient's own immune cells to fight a type of leukemia through a therapy called CAR-T.

The drug's maker, Novartis, plans to sell the treatment for $475,000 for the one-time dose.

The company said the price is actually below some independent estimates, including an appraisal from the United Kingdom's National Institute for Cost Effectiveness that pegged a cost-effective price between $600,000 and $750,000.

"We looked at the current standards of care, such as the cost of allogenic stem cell transplants, which is between $540,000-$800,000 for the first year in the U.S.," Novartis said in a statement to the Washington Examiner. "These external assessments as well as our own health economic analysis of the value of Kymriah, all indicated that a cost effective price would be $600,000 to $750,000."

Novartis said that by setting the price below that figure it could help to "support sustainability of the healthcare system and patient access while allowing a return for Novartis on our investment."

It added that it is working with the Centers for Medicare and Medicaid Services for a value-based approach to the drug. That would mean that CMS payments for medicine would be based on how well it works on patients.

But some advocates are upset at the high price tag.

"Kymriah's price tag is simply a continuation of the pattern of sky-high launch prices that spins further out of control each year," according to the Campaign for Sustainable Rx Pricing, an advocacy group that includes insurers, nurses, hospitals and doctors. "While we are very excited about the potential for CAR-T therapies to save lives, Novartis' pricing decision disappointingly pushes an unsustainable trend even closer to the breaking point."

Other groups are more heartened by Novartis' value-based purchasing agreement with CMS.

"While we await more specific details of the agreement reached between Novartis and CMS, we believe this arrangement will be a win for patients, as it recognizes the need to reward outcomes and ensure the cost of treatment is a reflection of its clinical success," said Joel White, president of the Council for Affordable Health Coverage, a coalition of employers, insurers and patient groups.

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Zika virus kills brain cancer stem cells – Washington University School of Medicine in St. Louis

Posted: at 9:49 am

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Virus potentially could be used to treat deadly disease

Brain cancer stem cells (left) are killed by Zika virus infection (image at right shows cells after Zika treatment). A new study shows that the virus, known for killing cells in the brains of developing fetuses, could be redirected to destroy the kind of brain cancer cells that are most likely to be resistant to treatment.

While Zika virus causes devastating damage to the brains of developing fetuses, it one day may be an effective treatment for glioblastoma, a deadly form of brain cancer. New research from Washington University School of Medicine in St. Louis and the University of California San Diego School of Medicine shows that the virus kills brain cancer stem cells, the kind of cells most resistant to standard treatments.

The findings suggest that the lethal power of the virus known for infecting and killing cells in the brains of fetuses, causing babies to be born with tiny, misshapen heads could be directed at malignant cells in the brain. Doing so potentially could improve peoples chances against a brain cancer glioblastoma that is most often fatal within a year of diagnosis.

We showed that Zika virus can kill the kind of glioblastoma cells that tend to be resistant to current treatments and lead to death, said Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine at Washington University School of Medicine and the studys co-senior author.

The findings are published Sept. 5 in The Journal of Experimental Medicine.

Each year in the United States, about 12,000 people are diagnosed with glioblastoma, the most common form of brain cancer. Among them is U.S. Sen. John McCain, who announced his diagnosis in July.

The standard treatment is aggressive surgery, followed by chemotherapy and radiation yet most tumors recur within six months. A small population of cells, known as glioblastoma stem cells, often survives the onslaught and continues to divide, producing new tumor cells to replace the ones killed by the cancer drugs.

In their neurological origins and near-limitless ability to create new cells, glioblastoma stem cells reminded postdoctoral researcher Zhe Zhu, PhD, of neuroprogenitor cells, which generate cells for the growing brain. Zika virus specifically targets and kills neuroprogenitor cells.

In collaboration with co-senior authors Diamond and Milan G. Chheda, MD, of Washington University School of Medicine, and Jeremy N. Rich, MD, of UC San Diego, Zhu tested whether the virus could kill stem cells in glioblastomas removed from patients at diagnosis. They infected tumors with one of two strains of Zika virus. Both strains spread through the tumors, infecting and killing the cancer stem cells while largely avoiding other tumor cells.

The findings suggest that Zika infection and chemotherapy-radiation treatment have complementary effects. The standard treatment kills the bulk of the tumor cells but often leaves the stem cells intact to regenerate the tumor. Zika virus attacks the stem cells but bypasses the greater part of the tumor.

We see Zika one day being used in combination with current therapies to eradicate the whole tumor, said Chheda, an assistant professor of medicine and of neurology.

To find out whether the virus could help treat cancer in a living animal, the researchers injected either Zika virus or saltwater (a placebo) directly into the brain tumors of 18 and 15 mice, respectively. Tumors were significantly smaller in the Zika-treated mice two weeks after injection, and those mice survived significantly longer than the ones given saltwater.

If Zika were used in people, it would have to be injected into the brain, most likely during surgery to remove the primary tumor. If introduced through another part of the body, the persons immune system would sweep it away before it could reach the brain.

The idea of injecting a virus notorious for causing brain damage into peoples brains seems alarming, but Zika may be safer for use in adults because its primary targets neuroprogenitor cells are rare in the adult brain. The fetal brain, on the other hand, is loaded with such cells, which is part of the reason why Zika infection before birth produces widespread and severe brain damage, while natural infection in adulthood causes mild symptoms.

The researchers conducted additional studies of the virus using brain tissue from epilepsy patients and showed that the virus does not infect noncancerous brain cells.

As an additional safety feature, the researchers introduced two mutations that weakened the viruss ability to combat the cells defenses against infection, reasoning that the mutated virus still would be able to grow in tumor cells which have a poor antiviral defense system but would be eliminated quickly in healthy cells with a robust antiviral response.

When they tested the mutant viral strain and the original parental strain in glioblastoma stem cells, they found that the original strain was more potent, but that the mutant strain also succeeded in killing the cancerous cells.

Were going to introduce additional mutations to sensitize the virus even more to the innate immune response and prevent the infection from spreading, said Diamond, who also is a professor of molecular microbiology, and of pathology and immunology. Once we add a few more changes, I think its going to be impossible for the virus to overcome them and cause disease.

Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, Fernandez E, Richner JM, Zhang R, Shan C, Wang X, Shi P-Y, Diamond MS, Rich JN, Chheda MG. Zika Virus Has Oncolytic Activity against Glioblastoma Stem Cells. The Journal of Experimental Medicine. Sept. 5, 2017.

This study was funded by the National Institutes of Health (NIH), grant numbers R01 AI073755, R01 AI104972, CA197718, CA154130, CA169117, CA171652, NS087913 and NS089272; the Pardee Foundation; the Concern Foundation; the Cancer Research Foundation and the McDonnell Center for Cellular and Molecular Neurobiology of Washington University.

Washington University School of Medicines 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Why are Bill Gates and Richard Branson investing in meat that costs $18000 a pound?, by Gene Marks – The Keene Sentinel

Posted: at 9:49 am

The world loves meat. So much so that demand for meat products is projected to grow by nearly 70 percent by 2050. But meat production places a significant strain on the planets resources. Research shows that todays meat-producing efforts use one-third of the Earths fresh water and land surface, and generate nearly one-fifth of all greenhouse gas emissions.

But thats not going to stop most of us from eating it because its too darn delicious. The founders behind San Francisco-based Memphis Meats know this, and theyre responding with what could be a disruptive change to the trillion-dollar meat production industry. Memphis Meats is making clean meat. Its also delicious. But theres one problem: It costs about $18,000 a pound.

Well, thats what it costs right now. The hope is that itll cost a lot less in the future. To get the price down to a more palatable level for consumers, the company just raised $17 million (to add to a previous $5 million invested) from the likes of Bill Gates, Richard Branson, and other tech and venture superstars, including food industry giants like Cargill. All of them are super-jazzed by the idea of clean meat.

So what is this stuff?

Its meat thats grown from stem cells in a lab. It uses about 1 percent of the land and 10 percent of the water needed to raise traditional animals and will mostly eliminate the need to feed, breed and slaughter livestock. Plus, the technology works-the company has already produced beef, chicken and duck from stem cells. But, of course, theres a lot more work to do. So the company will be using its newly raised cash to scale up operations and reduce production costs while staffing up-hiring chefs, scientists, creative and business people.

Meat demand is growing rapidly around the world. However, the way conventional meat is produced today creates challenges for the environment, animal welfare and human health, Uma Valeti, the companys chief executive said in a press release. Were going to bring meat to the plate in a more sustainable, affordable and delicious way.

Memphis Meats isnt the only company racing to produce meats in the lab. Competitors like Mosa Foods, Beyond Meats and Impossible Foods (recently featured in a Washington Post piece by Caitlin Dewey) are also working on lab-grown meat products for mass public commercialization. Theres still a long way to go, but the infant industry looks like a great opportunity for both future entrepreneurs and investors. In the meantime, just pass the A-1 sauce, please?

Gene Marks owns the Marks Group, a Bala Cynwyd, Pa.-based consulting firm and writes regularly for The Washington Posts On Small Business blog.

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