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Newswise — What if we could engineer a liver or kidney from a patient's own stem cells? How about helping regenerate tissue damaged by diseases such as osteoporosis and arthritis? A new UCLA study bring scientists a little closer to these possibilities by providing a better understanding how tissue is formed and organized in the body.

A UCLA research team discovered that migrating cells prefer to turn right when encountering changes in their environment. The researchers were then able to translate what was happening in the cells to recreate this left–right asymmetry on a tissue level. Such asymmetry is important in creating differences between the right and left sides of structures like the brain and the hand.

The research, a collaboration between the David Geffen School of Medicine at UCLA and the Center for Cell Control at UCLA's Henry Samueli School of Engineering and Applied Science, appears in the Feb. 17 issue of the journal Circulation Research.

"Our findings suggest a mechanism and design principle for the engineering of tissue," said senior author Dr. Linda L. Demer, a professor of medicine, physiology and bioengineering and executive vice chair of the department of medicine at the Geffen School of Medicine. "Tissue and organs are not simply collections of cells but require careful architecture and design to function normally. Our findings help explain how cells can distinguish and develop highly specific left–right asymmetry, which is an important foundation in tissue and organ creation."

Using microtechnology, the team engineered a culture surface in the lab with alternating strips of protein substrates that were cell-adhesive or cell-repellent, analogous to a floor with narrow horizontal stripes of alternating carpet and tile. Cells may encounter such surface changes when they travel through the body.
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The researchers observed that as the migrating cells crossed the interface between "carpet" and "tile" sections, they exhibited a significant tendency to turn right by 20 degrees, and, like a marching band, lined up in long, parallel rows, producing diagonal stripes over the entire surface.

"We had been noticing how these vascular cells would spontaneously form structures in cultures and wanted to study the process," said first author Ting-Hsuan Chen, a graduate student researcher in the department of mechanical and aerospace engineering at UCLA Engineering. "We had no idea our substrates would trigger the left–right asymmetry that we observed in the cells. It was completely unexpected.

"We found that cells demonstrated the ability to distinguish right from left and to self-organize in response to mechanical changes in the surfaces that they encounter. This provides insight into how to communicate with cells in their language and how to begin to instruct them to produce tissue-like architecture."

According to the researchers, the cells can sense the substrates beneath them, and this influences the direction of their migration and what shapes they form in the body. Of most interest, the researchers said, was the fact that the cells responded to the horizontal stripes by reorganizing themselves into diagonal stripes.

The team hopes to harness this phenomenon to use substrate interfaces to communicate with cells and instruct them to produce desired tissue structures for replacement. By adjusting the substrates, the researchers say, they have the potential to guide what structures the cells and tissue form.

The next stage of the research will be to control and guide cells to self-organize into two-dimensional and, eventually, three-dimensional patterns chosen by the researchers.

According to the research team, this is one of the first studies to demonstrate that encountering a change in substrate can trigger a cell's preference for turning left or right. It is also one of the first studies showing that cells can integrate left–right asymmetry into a patterned structure of parallel diagonal stripes resembling tissue architecture.

"Applications for this research may help in future engineering of organs from a patient's own stem cells," Demer said. "This would be especially important given the limited supply of donor organs for transplant and problems with immune rejection."

The study was funded by the National Science Foundation and National Institutes of Health.

Additional authors included Jeffrey J. Hsu, Alan Garfinkel and Yin Tintut from the UCLA Department of Medicine; Yi Huang and Chih-Ming Ho from the UCLA Department of Mechanical and Aerospace Engineering; Xin Zhao, Chunyan Guo and Zongwei Li from the

Institute of Robotics and Automatic Information System at China's Nankai University; and Margaret Wong from the UCLA Department of Bioengineering.

For more news, visit the UCLA Newsroom and follow us on Twitter.

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UCLA Discovery that Migrating Cells "Turn Right' has Implications for Engineering Tissues, Organs

LOS ANGELES--(BUSINESS WIRE)--

Investigators at The Saban Research Institute of Children’s Hospital Los Angeles have found that amniotic fluid stem cells (AFSC) can slow the progression of chronic kidney disease. A new study, published in the current issue of the Journal of the American Society of Nephrology, reveals that these stem cells can protect the kidneys and help maintain their function.

“We believe that this novel and innovative study clearly demonstrates the value and promise for amniotic fluid stem cells,” comments Roger De Filippo, MD, head of the GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics at The Saban Research Institute.

Using a model for Alport’s Syndrome, Dr. De Filippo’s team, which includes Dr. Laura Perin, one of the original investigators of AFSC and co-director of the GOFARR Laboratory, injected AFSC early in the course of the disease. Alport’s Syndrome is a kidney disease characterized by progressive renal fibrosis. Treatment with AFSC increased survival time and ameliorated the decline in kidney function.

Kidneys are responsible for filtering toxins from the blood. Chronic kidney disease (CKD) affects millions of children and adults in the United States. Characterized by a progressive decline in kidney function, CKD leads to an increase in health problems, including heart disease and diabetes. Those who develop end-stage kidney disease depend on dialysis to clear the waste from their blood and, ultimately, most patients require a kidney transplant in order to survive. With such stark long-term consequences, the new study offers hope to those suffering from the disease and is also a significant advancement in the stem cell research field.

Stem cell therapies have emerged over the last twenty years as a promising new area of biomedical research. While embryonic stem cells remain a controversial subject, AFSC are found in the fluid surrounding a fetus. The cells can be collected via amniocentesis or at birth without any harmful effects. This study demonstrates that the therapeutic benefit of AFSC is similar to that of embryonic stem cells.

“These findings are of significant interest to stem cell researchers. By using these common cells that are easily obtained, we can focus on other types of therapeutic studies that offer hope to many patients with chronic disabilities and disease,” says David Warburton, DSc, MD, director of the Developmental Biology and Regenerative Medicine Research program at The Saban Research Institute. This work was funded in part by a training grant from the California Institute for Regenerative Medicine, GOFARR and the Pasadena Guild of Children’s Hospital Los Angeles.

About Children’s Hospital Los Angeles

Children's Hospital Los Angeles has been named the best children’s hospital in California and among the best in the nation for clinical excellence with its selection to the prestigious US News & World Report Honor Roll. Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States, is one of America's premier teaching hospitals and has been affiliated with the Keck School of Medicine of the University of Southern California since 1932.

For more information, visit www.CHLA.org. Follow us on Twitter, Facebook, YouTube and LinkedIn, or visit our blog: http://www.WeAreChildrens.org.

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Investigators at The Saban Research Institute Demonstrate That Amniotic Fluid Stem Cells Can Slow Progression of ...

ScienceDaily (Feb. 16, 2012) — Scientists have found a way to generate and maintain stem cells much more efficiently by amplifying the effect of an essential protein.

Researchers from Denmark, Scotland and the USA have created synthetic versions of a protein, which manipulates adult cells -- such as skin cells -- so that they can subsequently revert to an earlier, embryonic like state. These reverted cells have the potential to become any cell in the body.

As well as reverting adult cells to this state -- known as induced pluripotent stem cells , the protein also plays a key role in maintaining embryonic stem cells in a pure form. If the protein -- Oct4 -- is not present, the embryonic stem cells will start to differentiate into specific cells.

In order to reprogamme adult cells to have stem cell properties viruses need to be added to cell cultures to trigger production of significant quantities of Oct4.

Oct4 plays a powerful role in regulating stem cell genes. However, while large quantities of Oct4 are needed too much of it can ruin the properties of stem cells.

Scientists, whose work is published in the journal Cell Reports, were able to overcome this by producing a synthetic version of Oct4 that amplified the effect of the protein in its natural form.

The synthetic version of Oct4 was much more efficient in turning on genes that instruct cells on how to be stem cells and, as a result, the cells did not need as much Oct4 for either reprogramming or to remain as stem cells -- thereby eliminating problems caused by too much Oct4.

In fact, the synthetic Oct4 could support stem cells under conditions that they do not normally grow. These findings could also help scientists find new ways generate stem cells in the laboratory.

The study showed that Oct4 was mainly responsible for turning on genes that instruct cells on how to become stem cells, rather than turning off genes that encourage the cells to differentiate.

"Our discovery is an important step towards generating and maintaining stem cells much more effectively," says Professor Joshua Brickman, affiliated with both The Danish Stem Cell Center (DanStem), University of Copenhagen and Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh.

"Embryonic stem cells are characterized, among other things, by their ability to perpetuate themselves indefinitely and differentiate into all the cell types in the body -- a trait called pluripotency. But to be able to use them medically, we need to be able to maintain them in a pure state, until they're needed. When we want to turn a stem cell into a specific cell, such as insulin producing beta cell, or a nerve cell in the brain, we'd like this process to occur accurately and efficiently. This will not be possible if we don't understand how to maintain stem cells as stem cells. As well as maintaining embryonic stem cells in their pure state more effectively, the artificially created Oct4 was also more effective at reprogramming adult cells into so-called induced Pluripotent Stem cells, which have many of the same traits and characteristics as embryonic stem cells but can derived from the patients to both help study degenerative disease and eventually treat them."

Oct4 is a so-called transcription factor -- a protein that binds to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to mRNA. The synthetic version of Oct4 was created by using recombinant DNA technology whereby a gene was modified to produce new and more active protein. The modified gene was either introduced into stem cells or used to reprogram adult skin cells.

If scientists can exploit this programming of stem cell programs, it will improve the ability to generate stem cells directly from a patient. These cells could in turn potentially be used for individualised studies and for developing individualized therapies for degenerative diseases such as type 1 diabetes and neuro-degenerative diseases.

The study involved mouse embryonic stem cells, early embryonic progenitors cells in frogs as well as iPS cells from both mouse and human sources. The research was supported by grants from the Novo Nordisk Foundation (DK), the Medical Reseach Council and the Biotechnology and Biological Sciences Research Council (MRC and BBSRC, UK).

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The above story is reprinted from materials provided by University of Edinburgh.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Fella Hammachi, Gillian M. Morrison, Alexei A. Sharov, Alessandra Livigni, Santosh Narayan, Eirini P. Papapetrou, James O'Malley, Keisuke Kaji, Minoru S.H. Ko, Mark Ptashne, Joshua M. Brickman. Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency. Cell Reports, 2012; DOI: 10.1016/j.celrep.2011.12.002

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Synthetic protein amplifies genes needed for stem cells

LOS ANGELES--(BUSINESS WIRE)--

ImmunoCellular Therapeutics, Ltd. (“ImmunoCellular” or the “Company”) (OTCBB: IMUC –News), a biotechnology company focused on the development of novel immune-based cancer therapies, today announced that John Yu, MD, Chairman and Chief Scientific Officer of ImmunoCellular Therapeutics, will deliver a presentation at the Cambridge Healthtech Institute’s inaugural Targeting Stem Cells Symposium as a part of the 19th Annual Molecular Medicine Tri-Conference from February 19-23, 2012. Dr. Yu will present during a session highlighting Emerging Cancer Stem Cell Therapeutics, featuring the Company’s discovery and development of cancer stem cell therapy.

The Cambridge Healthtech Institute’s Targeting Cancer Stem Cells Symposium reflects a growing interest in cancer stem cells and their developing importance in the field of oncology, as more pharmaceutical and biotech companies have begun to focus on cancer stem cells as oncological drug targets. The symposium will feature case studies from those working with cancer stem cells, a history of the role of cancer stem cells in treatment resistance, as well as highlights from ongoing novel cancer stem cell therapeutic development programs and platforms.

About ImmunoCellular Therapeutics, Ltd.

IMUC is a Los Angeles-based clinical-stage company that is developing immune-based therapies for the treatment of brain and other cancers. The Company recently commenced a Phase II trial of its lead product candidate, ICT-107, a dendritic cell-based vaccine targeting multiple tumor associated antigens including those associated with cancer stem cells for glioblastoma treatment. To learn more about IMUC, please visit www.imuc.com.

Forward-Looking Statements

This press release contains certain forward-looking statements that are subject to a number of risks and uncertainties, including the risk that any patents issued covering IMUC’s vaccine technology will not provide significant commercial protection for IMUC’s technology or products; the risk that the safety and efficacy results obtained in the Phase I trial for the dendritic cell- based vaccine will not be confirmed in subsequent trials; the risk that the correlation between immunological response and progression-free and overall survival in the Phase I trial for ICT-107 will not be reflected in statistically significant larger patient populations; the risk that IMUC will not be able to secure a partner company for development or commercialization of ICT-107. Additional risks and uncertainties are described in IMUC's most recently filed SEC documents, such as its most recent annual report on Form 10-K, all quarterly reports on Form 10-Q and any current reports on Form 8-K. IMUC undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

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ImmunoCellular Therapeutics To Present at Targeting Stem Cells Symposium during 19th Annual Molecular Medicine Tri ...

SAN BRUNO, Calif., Feb. 16, 2012 /PRNewswire/ -- Cord Blood Registry (CBR) is the exclusive partner for a growing number of clinical researchers focusing on the use of a child's own cord blood stem cells to help treat pediatric brain injury and acquired hearing loss. To ensure consistency in cord blood stem cell processing, storage and release for infusion, three separate trials have included CBR in their FDA-authorized protocol—including two at the University of Texas Health Science Center at Houston (UTHealth) working in partnership with Children's Memorial Hermann Hospital, and a third at Georgia Health Sciences University, home of the Medical College of Georgia (MCG). This makes CBR the only family stem cell bank pairing researchers with prospective patients for these studies. 

(Logo: http://photos.prnewswire.com/prnh/20120216/AQ54476LOGO)

"Partnering with a series of specialists who want to research the use of a child's own newborn blood stem cells on a variety of disease states allows CBR to help advance medical research for regenerative therapies by connecting the child whose family banked with CBR to appropriate researchers," said Heather Brown, MS, CGC, Vice President of Scientific & Medical Affairs at Cord Blood Registry.  "The pediatric specialists from UTHealth, Children's Memorial Hermann Hospital, and Georgia Health Sciences University are at the forefront of stem cell research as they evaluate cord blood stem cells' ability to help facilitate the healing process after damage to nerves and tissue."

Hearing Loss and Traumatic Brain Injury Clinical Trials Break New Ground

Sensorineural hearing loss affects approximately 6 per 1,000 children by 18 years of age, with 9 percent resulting from acquired causes such as viral infection and head injury.(1,2,3)  The Principal Investigator of the hearing loss study is Samer Fakhri, M.D., surgeon at Memorial Hermann-Texas Medical Center and associate professor and program director in the Department of Otorhinolaryngology – Head & Neck Surgery at UTHealth.  He is joined by James Baumgartner, M.D., sponsor of the study and guest research collaborator for this first-of-its-kind FDA-regulated, Phase 1 safety study of the use of cord blood stem cells to treat children with acquired hearing loss. The trial follows evidence from published studies in animals that cord blood treatment can repair damaged organs in the inner ear. Clients of CBR who have sustained a post-birth hearing loss and are 6 weeks to 2 years old may be eligible for the year-long study. "The window of opportunity to foster normal language development is limited," said James Baumgartner, M.D.  "This is the first study of its kind with the potential to actually restore hearing in children and allow for more normal speech and language development."

Although the neurologic outcome for nearly all types of brain injury (with the exception of abuse) is better for children than adults,(4,5) trauma is the leading cause of death in children,(6) and the majority of the deaths are attributed to head injury.(7) Distinguished professor of pediatric surgery and pediatrics at UTHealth, Charles S. Cox, M.D. launched an innovative study building on a growing portfolio of research using stem cell-based therapies for neurological damage. The study will enroll 10 children ages 18 months to 17 years who have umbilical cord blood banked with CBR and have suffered a traumatic brain injury (TBI) and are enrolled in the study within 6-18 months of sustaining the injury. Read more about the trial here.

"The reason we have become interested in cord blood cells is because of the possibility of autologous therapy, meaning using your own cells. And the preclinical models have demonstrated some really fascinating neurological preservation effects to really support these Phase 1 trials," says Charles S. Cox, M.D., principle investigator of the trial. "There's anecdotal experience in other types of neurological injuries that reassures us in terms of the safety of the approach and there are some anecdotal hints at it being beneficial in certain types of brain injury."

Georgia Health Sciences University (GHSU) Focuses on Cerebral Palsy

At the GHSU in Augusta, Dr. James Carroll, professor and chief of pediatric neurology, embarked on the first FDA-regulated clinical trial to determine whether an infusion of stem cells from a child's own umbilical cord blood can improve the quality of life for children with cerebral palsy. The study will include 40 children whose parents have stored their cord blood at CBR and meet inclusion criteria. 

"Using a child's own stem cells as a possible treatment is the safest form of stem cell transplantation because it carries virtually no threat of immune system rejection," said Dr. Carroll. "Our focus on cerebral palsy breaks new ground in advancing therapies to change the course of these kinds of brain injury—a condition for which there is currently no cure."

Cerebral palsy, caused by a brain injury or lack of oxygen in the brain before birth or during the first few years of life, can impair movement, learning, hearing, vision and cognitive skills. Two to three children in 1,000 are affected by it, according to the Centers for Disease Control.(8)

Cord Blood Stem Cell Infusions Move From the Lab to the Clinic

These multi-year studies are a first step to move promising pre-clinical or animal research of cord blood stem cells into clinical trials in patients. Through the CBR Center for Regenerative Medicine, CBR will continue to partner with physicians who are interested in advancing cellular therapies in regenerative applications.

"The benefits of cord blood stem cells being very young, easy to obtain, unspecialized cells which have had limited exposure to environmental toxins or infectious diseases and easy to store for long terms without any loss of function, make them an attractive source for cellular therapy researchers today," adds Brown. "We are encouraged to see interest from such diverse researchers from neurosurgeons to endocrinologists and cardiac specialists."

About CBR

CBR® (Cord Blood Registry®) is the world's largest and most experienced cord blood bank.  The company has consistently led the industry in technical innovations and supporting clinical trials. It safeguards more than 400,000 cord blood collections for individuals and their families. CBR was the first family bank accredited by AABB and the company's quality standards have been recognized through ISO 9001:2008 certification—the global business standard for quality. CBR has also released more client cord blood units for specific therapeutic use than any other family cord blood bank. Our research and development efforts are focused on helping the world's leading clinical researchers advance regenerative medical therapies. For more information, visit http://www.cordblood.com.

(1)  Bergstrom L, Hemenway WG, Downs MP. A high risk registry to find congenital deafness. Otolaryngol Clin North Am. 1977;4:369-399.
(2)  Billings KR, Kenna MA. Causes of pediatric sensorineural hearing loss: yesterday and today. Arch Otolaryngol Head Neck Surg. 1999 May;125(5):517-21.
(3)  Smith RJ, Bale JF Jr, White KR. Sensorineural hearing loss in children. Lancet. 2005;365(9462):879-890.
(4)  Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.
(5)  Schnitzer, Patricia, PH.D., "Prevention of Unintentional Childhood Injuries", American Academy of Family Physicians, 2006.
(6)  Centers for Disease Control and Prevention, "10 Leading Causes of Death, United States, 1997-2007", WISQARS, National Center for Health Statistics (NCHS), National Vital Statistics System
(7)  Marquez de la Plata, Hart et al, National Institutes of Health, "Impact of Age on Long-term Recovery From Traumatic Brain Injury", Arch Phys Med Rehabilitation, May 2008.
(8)  Centers for Disease Control and Prevention, http://www.cdc.gov/Features/dsCerebralPalsy, accessed February 6, 2012

Go here to read the rest:
Groundbreaking Clinical Trials Study Cord Blood Stem Cells to Help Treat Brain Injury and Hearing Loss

A UCLA research team discovered that migrating cells prefer to turn right when encountering changes in their environment. The researchers were then able to translate what was happening in the cells to recreate this left–right asymmetry on a tissue level. Such asymmetry is important in creating differences between the right and left sides of structures like the brain and the hand.

The research, a collaboration between the David Geffen School of Medicine at UCLA and the Center for Cell Control at UCLA's Henry Samueli School of Engineering and Applied Science, appears in the Feb. 17 issue of the journal Circulation Research.

"Our findings suggest a mechanism and design principle for the engineering of tissue," said senior author Dr. Linda L. Demer, a professor of medicine, physiology and bioengineering and executive vice chair of the department of medicine at the Geffen School of Medicine. "Tissue and organs are not simply collections of cells but require careful architecture and design to function normally. Our findings help explain how cells can distinguish and develop highly specific left–right asymmetry, which is an important foundation in tissue and organ creation."

Using microtechnology, the team engineered a culture surface in the lab with alternating strips of protein substrates that were cell-adhesive or cell-repellent, analogous to a floor with narrow horizontal stripes of alternating carpet and tile. Cells may encounter such surface changes when they travel through the body.

The researchers observed that as the migrating cells crossed the interface between "carpet" and "tile" sections, they exhibited a significant tendency to turn right by 20 degrees, and, like a marching band, lined up in long, parallel rows, producing diagonal stripes over the entire surface.

"We had been noticing how these vascular cells would spontaneously form structures in cultures and wanted to study the process," said first author Ting-Hsuan Chen, a graduate student researcher in the department of mechanical and aerospace engineering at UCLA Engineering. "We had no idea our substrates would trigger the left–right asymmetry that we observed in the cells. It was completely unexpected.

"We found that cells demonstrated the ability to distinguish right from left and to self-organize in response to mechanical changes in the surfaces that they encounter. This provides insight into how to communicate with cells in their language and how to begin to instruct them to produce tissue-like architecture."

According to the researchers, the cells can sense the substrates beneath them, and this influences the direction of their migration and what shapes they form in the body. Of most interest, the researchers said, was the fact that the cells responded to the horizontal stripes by reorganizing themselves into diagonal stripes.

The team hopes to harness this phenomenon to use substrate interfaces to communicate with cells and instruct them to produce desired tissue structures for replacement. By adjusting the substrates, the researchers say, they have the potential to guide what structures the cells and tissue form.

The next stage of the research will be to control and guide cells to self-organize into two-dimensional and, eventually, three-dimensional patterns chosen by the researchers.

According to the research team, this is one of the first studies to demonstrate that encountering a change in substrate can trigger a cell's preference for turning left or right. It is also one of the first studies showing that cells can integrate left–right asymmetry into a patterned structure of parallel diagonal stripes resembling tissue architecture.

"Applications for this research may help in future engineering of organs from a patient's own stem cells," Demer said. "This would be especially important given the limited supply of donor organs for transplant and problems with immune rejection."

Provided by University of California - Los Angeles

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Discovery that migrating cells 'turn right' has implications for engineering tissues, organs