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Skin Cells May One Day Generate Embryonic Stem Cells [2/17/2007]

Adapted from the Howard Hughes Medical Institute

Healthy and viable mice that survive until adulthood have, for the first time, been cloned from adult stem cells. Scientists from Rockefeller University, including Howard Hughes Medical Institute investigator Elaine Fuchs, used cells called keratinocyte stem cells, which represent a new model system for cloning. Keratinocytes come from the skin, making them a particularly attractive stem cell source because of their ready accessibility. One day, they could be used to tailor therapies, as well as to better understand and treat diseases.

While the new research shows that adult skin stem cells can be a promising starting point for cloning mice, Fuchs said she is more enthusiastic about these cells' potential for generating embryonic stem cells. Instead of implanting blastocysts and cloning mice, the blastocysts can be cultured in the laboratory to generate embryonic stem cells. In theory, these embryonic stem cells could be coaxed into producing any other type of cell, from neurons to muscle cells to skin cells. Fuchs said that is the use of nuclear transfer technology that researchers would like translate to humans. All it would involve, she pointed out, is an unfertilized egg cell, a skin biopsy, and a tissue culture dish. If embryonic stem cells can be generated from a patient's skin, and then used to create cells or tissues according to the patient's specific need, the problem of immune rejection might be circumvented. “As importantly, these cells would also allow scientists to study the disease,� said Fuchs.

Fuchs cautioned that human applications are far in the future. “We don't have the capability of generating human embryonic stem cells from skin cells, and scientists are still learning how to differentiate embryonic stem cells into different cell types, such as particular types of neurons or pancreatic islet cells,� she said.

Fuchs and her colleague Peter Mombaerts published their laboratories' findings online February 12, 2007, in the Proceedings of the National Academy of Sciences.

The Stem Cell Research Foundation is proud to be supporting Dr. Fuch’s for the following research project: Stem Cells from Different Stratified Epithelial Tissues (April 1, 2005 – March 31, 2007).


Human Stem Cell Transplants Mature Into Neurons And Make Contacts In Rat Spinal Cord [2/17/2007]

Adapted from Johns Hopkins Medical Institutions

Human nerve stem cells transplanted into rats' damaged spinal cords have survived, grown and in some cases connected with the rats' own spinal cord cells in a Johns Hopkins laboratory, overturning the long-held notion that spinal cords won't allow nerve repair.

A report on the experiments will be published online this week at PLoS Medicine and "establishes a new doctrine for regenerative neuroscience," says Vassilis Koliatsos, M.D., associate professor of neuropathology at Johns Hopkins. "The spinal cord, a part of the nervous system that is thought of as incapable of repairing itself, can support the development of transplanted cells," he added. "We don't yet know whether the connections we've seen can transmit nerve signals to the degree that a rat could be made to walk again," says Koliatsos, "We're still in the proof of concept stage, but we're making progress and we're encouraged."

In their experiments, the scientists gave anesthetized rats a range of spinal cord injuries to lesion or kill motor neurons or performed sham surgeries. They varied experimental conditions to see if the presence or absence of spinal cord lesions had an effect on the survival and maturation of human stem cell grafts. Two weeks after lesion or sham surgery, they injected human neural stem cells into the left side of each rat's spinal cord.

After six months, the team found more than three times the number of human cells than they injected in the damaged cords, meaning the transplanted cells not only survived but divided at least twice to form more cells. Moreover, says Koliatsos, the cells not only grew in the area around the original injection, but also migrated over a much larger spinal cord territory.

Three months after injection, the researchers found evidence that some of the transplanted cells developed into support cells rather than nerve cells, while the majority became mature nerve cells. High-powered microscopic examination showed that these nerve cells appear to have made contacts with the rat's own spinal cord cells.

Movement Of Stem Cells Pave Way For Brain Research [2/17/2007]

Adapted from The University of Auckland

Scientists have discovered how new brain cells migrate throughout the brain, a finding which opens the way for new treatments of diseases such as Alzheimer’s, Parkinson’s and Huntington’s.

Research from The University of Auckland, alongside colleagues in Sweden, has identified how stem cells, immature cells that have not yet developed specific specialized functions, move from the site of generation in the brain, to other areas including those affected by neurological diseases. "We’ve known about the migration of brain cells in mammals for some years but humans have usually been deemed different," says Professor Richard Faull of the University’s Faculty of Medical and Health Sciences. "Our studies show that stem cells migrate long distances through the human brain in order to replace cells that die in the olfactory system. Utilization of this migration may allow us to direct the stem cells to other brain regions that are affected by brain cell loss. In addition, our study looked at adult brain tissue, which means much of the brain’s ability to regenerate remains active even in older human brains.

"This research will change the way in which we can look at diseases where brain cells die, such as Huntington’s disease, or require repair, such as stroke. By knowing how stem cells move around, we can now look at new ways to regenerate cells and repair damage to the areas of the brain affected by these conditions."

Their findings have been published in the journal Science.


World’s First Adult Stem Cell Study Using Patient’s Own Fat Tissue For Treating Heart Failure Begins This Week [2/7/2007]

Adapted from the Texas Heart Institute

For the first time in humans, a heart failure patient received adult stem cells—taken from his own adipose (fat) tissue—which were processed and injected directly into the heart muscle with a special catheter.

The trial site for the study is Hospital General Universitario Gregorio Marañón in Madrid, Spain. Dr. Fernandez-Avilés, Professor of Cardiovascular Medicine and Chief of Cardiology Service at Gregorio Marañón and Dr. Perin, Director of New Interventional Cardiovascular Technology and Director of Stem Cell Center at the Texas Heart Institute at St. Luke’s will serve as co-principal investigators.

The procedure involves removing adult stem cells from fat tissue just as in a liposuction procedure. The cells are processed with a proprietary process developed by Cytori Therapeutics, Inc. After about one hour of processing, the stem cells are injected directly into damaged but viable areas of the heart muscle through an investigational device called a NOGA catheter. This catheter allows three-dimensional color-coded maps of the mechanical and electrical function of the heart’s left ventricle.

“This is the first time we have used adipose-derived stem cells in humans. We had good results in our pre-clinical tests and we are excited about taking this research to the next level,� said Dr. Perin.

A variety of clinical functional and imaging endpoints will be assessed in the study. The outcomes of the study will be evaluated after a six month follow up. The doctors expect to present the six month outcomes of the study in 2008.

Heart failure is a condition in which the heart can’t adequately pump sufficient blood to the body’s other organs. It is the only cardiovascular condition which continues to rise in the U.S. More than half a million Americans are diagnosed with heart failure each year.

Researchers Safely Regenerate Failing Mouse Hearts With Programmed Embryonic Stem Cells [2/28/2007]
Adapted from the Mayo Clinic, Rochester

Mayo Clinic researchers have safely transplanted cardiac preprogrammed embryonic stem cells into diseased hearts of mice successfully regenerating damaged heart muscle without precipitating the growth of a cancerous tumor—which, so far, has impeded successful translation into practice of embryonic stem cell research.

The Mayo study is the first known report establishing a successful, tumor-resistant approach to growing new heart tissue from an embryonic stem cell source. The study is published in the February issue of the Journal of Experimental Medicine.

Embryonic stem cells have the potential to become any cell type in the body. But directing the stem cells to regenerate targeted tissue is a process that hasn't yet been perfected. Scientists continue to closely scrutinize stem cell strategies to establish even safer and more effective treatments for disease.

"Embryonic stem cells are like a stealth fighter jet that flies virtually undetectable by radar," says the study's first author, Atta Behfar, M.D., Ph.D., a clinician-investigator fellow in the Mayo Graduate School of Medicine. "The host body doesn't recognize embryonic stem cells, which it allows to multiply freely in an unimpeded fashion."

The Mayo study is the first known report of a successful strategy for programming embryonic stem cells to suppress cancer genes, to mature into heart cells (also known as cardiomyocytes) and to successfully fix injured hearts without causing tumors to develop. The study removes a critical obstacle towards translation of regenerative technology into developing new therapies for people with heart disease.

"Embryonic stem cells have an unequaled potential for repair, yet it has been uncertain whether we can drive them to safely regenerate the tissue we would like to replace," says Andre Terzic, M.D., Ph.D., a stem cell specialist and lead investigator of the study. "Our objective was to repair heart muscle by avoiding the limitations intrinsic to embryonic stem cells, i.e., potential tumor growth.

"In this study, we have successfully programmed embryonic stem cells to safely generate new cardiac muscle tissue, leading potentially to new therapy," Dr. Terzic says.

"Our goal is to apply these findings to adult stem cells, and in our next step create the first human cardioprogenitor stem cells as a tool for therapies in the future," Dr. Terzic says.

Mice Cloned From Skin Cells [2/17/2007]

Adapted from the Howard Hughes Medical Institute

Healthy and viable mice that survive until adulthood have, for the first time, been cloned from adult stem cells. Scientists from Rockefeller University, including Howard Hughes Medical Institute investigator Elaine Fuchs, used cells called keratinocyte stem cells, which represent a new model system for cloning. Keratinocytes come from the skin, making them a particularly attractive stem cell source because of their ready accessibility. One day, they could be used to tailor therapies, as well as to better understand and treat diseases.

While the new research shows that adult skin stem cells can be a promising starting point for cloning mice, Fuchs has indicated she is more enthusiastic about the potential of these cells for generating embryonic stem cells. Instead of implanting blastocysts and cloning mice, the blastocysts can be cultured in the laboratory to generate embryonic stem cells. In theory, these embryonic stem cells could be coaxed into producing any other type of cell, from neurons to muscle cells to skin cells. Fuchs said that it is the use of nuclear transfer technology that researchers would like to translate to humans. This would only involve an unfertilized egg cell, a skin biopsy, and a tissue culture dish. If embryonic stem cells can be generated from a patient's skin, and then used to create cells or tissues according to the patient's specific need, the problem of immune rejection might be circumvented. “As importantly, these cells would also allow scientists to study the disease,� said Fuchs.

Fuchs cautioned that human applications are far in the future. “We don't have the capability of generating human embryonic stem cells from skin cells, and scientists are still learning how to differentiate embryonic stem cells into different cell types, such as particular types of neurons or pancreatic islet cells,� she said.

Fuchs and her colleague, Peter Mombaerts, published their findings online February 12, 2007 in the Proceedings of the National Academy of Sciences.
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