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catalyst

The Magazine of The College of Sciences

Illustration by Stephen Durke

Regenerate It: The Power of Progenitor Cells

Stem cells offer alternatives to traditional medical techniques


Here is a bold vision for the future of medicine: A soldier, before deploying to the battlefield, will leave a sample of his or her cells at a special biomedical bank. There, the cells will be induced with advanced techniques to turn into stem cells – the type of cell that could later be stimulated to produce any tissue in the body. If the soldier is injured in battle, medical specialists will coax the soldier’s own stem cells into producing the specialized tissue that he or she needs -- skin, bone, muscle, blood vessels or vital organs. These then can be implanted, thereby healing the wounds of war with tissues that will not face rejection by the body.

Regenerative medicine, as it is called, is a promising vision now in its infancy. Still, some of San Antonio’s forward-looking scientists, including John McCarrey, Ph.D., director of the San Antonio Institute for Cellular and Molecular Primatology, and Jane and Roland Blumberg Professor of Biology say that San Antonio is perfectly poised to become a global center for this emerging field. McCarrey and colleage Christopher Navara, associate professor of biology, are stem cell biologists working with the Texas Biomedical Research Institute and Harvard University on a plan that could turn UTSA and the city of San Antonio into a hub for developing and testing stem cell therapies.

Texas Biomed – which had been known as Southwest Foundation for Biomedical Research until February of this year – is home to the federally supported Southwest National Primate Research Center, where a large colony of pedigreed baboons already is used to study common human diseases like diabetes, heart disease and arthritis. That makes the animals a viable research model for the early work that will be necessary before stem cell therapies addressing these conditions are ready for human clinical trials.

“Baboons are the most clinically relevant animal model for testing stem cell procedures and therapies for many diseases— testing that needs to be done to optimize the efficacy and safety of stem cells before we put them into people,” McCarrey said.

“There are a lot of people who want to do this: clinical researchers who are experts in treating heart disease or diabetes or spinal cord injuries, who don’t have experience with stem cells and don’t have access to primates,” McCarrey said. “That is where we come in. We are prepared to set up a resource to work with these disease experts and test therapies as they are developed.”

Stem cells are progenitor cells - powerful cells that, under the right conditions, can become different tissues in the body

Stem cells are progenitor cells—powerful cells that, under the right conditions, can become different tissues in the body. As adults, humans produce stem cells that have some ability to differentiate and repair tissues within the body. But the most potent stem cells are the undifferentiated cells found in an embryo right after fertilization. These cells are pluripotent; as fetal development continues, they give rise to every tissue in the body.

Research involving human embryonic stem cells remains an ethical controversy because the embryo is destroyed when the stem cells are harvested, but there is another option. Recent advances in the field have established a new standard for stem cell research—using cells from adults instead of from embryos.

In the past five years research teams around the world have learned how to turn back the clock on mature cells that already have become specialized. In 2006, researchers in Japan demonstrated that they could manipulate mouse cells and make them pluripotent, like embryonic cells. A year later, independent teams from Harvard and Japan demonstrated that they could induce human adult cells to do the same thing.

Induced pluripotent stem cells, iPS, as they are called, eliminate the ethical complications of working with embryonic stem cells. Plus, since they come from adults, they open the door for the new field of regenerative and personalized medicine, in which a patient’s own cells can be stimulated to produce cells to repair blood vessels, skin, damaged organs or even spinal cords and brain tissue.

But so far scientists have shown only that they can produce these powerful cells. That is just the first half of a complex puzzle, McCarrey said.

“The back half of this is delivering them back into the body,” McCarrey said.

A multitude of questions are still to be answered about these cells and the potential treatments. What is the best way to deliver stem cells back into to the body? How do doctors get them to express the correct genes, in the correct location? Will they solve one medical problem without causing others? There are concerns that induced pluripotent cells will cause cancer, because of the genetic manipulation used to produce them. Researchers must demonstrate that they are safe.

“All of this back half of the science needs to be tested in an animal model before we start implanting these iPS cells into humans,” McCarrey said.

At Southwest Regional Primate Research Center, scientists have studied baboons for 50 years. The animals have been models for human diseases like atherosclerosis, obesity, diabetes, arthritis and more. About 1,500 baboons are part of a unique pedigreed colony, for which scientists have maintained meticulous health, breeding and genetic records for six generations. Scientists have developed a genetic linkage map for the baboon, a powerful tool for locating genes that underlie susceptibility to disease.

The chronic diseases that have been studied in baboons are amenable to treatment with stem cell therapies, said John VandeBerg, Ph.D., director of the primate center and the chief scientific officer of Texas Biomed. The animals are genetically and physiologically very similar to humans. Stem cell procedures and therapies can be developed and tested in baboons first and, if they work, moved forward quickly into human clinical trials, he said.

“A lot has been done with mice and we have learned a lot about organ development and how tissues heal,” VandeBerg said. “But the mouse is a far different creature from a human, and what you can do in a mouse does not necessarily translate into a human.”

The scientists have applied for a National Institutes of Health grant to support their start-up efforts. They will find out in summer 2011 whether the federal funds are forthcoming.

But research work already is underway. UTSA and Texas Biomed have joined forces with the University of Texas Health Science Center to establish the San Antonio Institute of Molecular and Cellular Primatology. Together they are working with primate embryonic stem cells and are learning how to induce mature baboon cells into a pluripotent state.

UTSA also has added faculty and facilities in support of the stem cell biology program, noted George Perry, Ph.D., dean of the College of Sciences. Three scientists have been recruited to join McCarrey’s team in the past year. San Antonio philanthropic institutions – the Max and Minnie Tomerlin Voelcker Fund and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation – have made gifts to recruit scientists and set up a core lab.

"This will be another important piece that will move us forward to becoming a Tier One research university and to making important discoveries."

- George Perry, Ph.D., dean of the College of Sciences

Such support demonstrates UTSA’s commitment to building a world class science program, Perry said. “This will be another important piece that will move us forward to becoming a Tier One research university and to making important discoveries,” he said.

The scientists expect to draw other regional expertise into their collaboration. Clinical practitioners at the University of Texas Health Science Center, tissue engineers from Southwest Research Institute and military medical researchers all have potential roles, VandeBerg and McCarrey said. The military is expanding its medical treatment and research capacity at Fort Sam Houston and Brooke Army Medical Center, McCarrey noted.

“The military is very interested in regenerative medicine for wound care and burn care,” he added.

Already, Perry noted, private companies are taking note and exploring options for setting up operations in San Antonio.

“This will be very good for the community,” said Bernard Arulanandam, Ph.D., associate dean of research for scientific innovation and Jane and Roland Blumberg Professor of Biology. “We can build our center of excellence as a global center for stem cell innovations. This is one area where we have all the key ingredients.”

McCarrey agreed. “There is huge potential for San Antonio to jump in to become a major player in this field because we have this unique combination of resources.”

Other medical centers and universities also are working on developing research protocols with other animal models, McCarrey noted. But he thinks San Antonio has the right approach and the right combination of resources to make the biggest impact in this emerging field. The venture includes Harvard’s pluripotent stem cell expertise, the nonhuman primate disease models at Texas Biomed, and the laboratory and clinical experience of UTSA, the health science center and Brooke Army Medical Center.

"There is huge potential for San Antonio to jump in to become a major player in this field because we have this unique combination of resources"

- John McCarrey, Ph.D., director of the San Antonio Institute for Cellular and Molecular Primatology

McCarrey expects researchers from other universities and medical centers will bring work to San Antonio as well. “What we are trying to generate is a user-friendly resource so anybody from around the country who wants to do tests in baboonspecific stem cells would be able to get together with us to set up their experiments,” he said. “We want this resource to be useful to the entire scientific community.”

In the future, this research will transform medicine. VandeBerg sees the day when regenerative therapies will offer treatments for devastating spinal cord injuries and degenerative neurological conditions like Parkinson’s and Alzheimer’s diseases. Treatment of broken bones, burns and wounds all will be improved by stem cell therapies. Treatments for chronic diseases of aging like cardiovascular disease and arthritis will enable people to live longer and healthier lives.

“I believe stem cell medicine is going to revolutionize clinical care over the next half century,” VandeBerg said. “I think it will do as much for reducing sickness and death as antibiotics and vaccines did.”

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