Advances in stem cell research

Mar 8 2009

Scientists at The University of Texas Health Science Center at Houston are on the forefront of stem cell research, developing novel therapies designed to generate heart cells, repair traumatic lung injuries, grow new bone and stanch the spread of cancer cells.

Research at the UT Health Science Center at Houston is focused on embryonic stem cells and adult stem cells. A stem cell is a generic cell that has the potential to develop into a specialized cell type and to make copies of itself through cell division. The process of cell specialization is called differentiation.

Human embryonic stem cells are highly versatile and have the potential to develop into any cell type in the body with the exception of the placenta. According to the National Institutes of Health (NIH), they are extracted from clusters of cells called blastocysts that are created during in vitro fertilization procedures to help people with reproductive issues. The cells are sometimes donated for the purposes of research with the permission of the donors.

Adult stem cells come from umbilical cord blood, bone marrow and many other tissues. While less versatile, they have been used in medical procedures for many decades including bone marrow transplants, where bone marrow stem cells are used to treat leukemia and other cancers to replenish blood cells.

Researchers at the Health Science Center use human embryonic stem cells approved by the NIH.

Embryonic stem cell research

Nobel Laureate and UT Health Science Center at Houston Professor Ferid Murad, M.D., Ph.D., is applying his award-winning research into the properties of a signaling molecule called nitric oxide to further the understanding of the differentiation process for human embryonic stem cells. Murad and his colleagues were the first to report that nitric oxide acts to increase the diameter of blood vessels in the body.

Murad was one of the first in the Texas Medical Center to work with embryonic stem cells and to obtain NIH grant support. Over the last four years, his lab has received about $1.2 million from the NIH to study the signals that change human embryonic stem cells into brain and heart cells. Results have been published in five scholarly articles. He is director emeritus of the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the Health Science Center.

In a December issue of the Proceedings of the National Academy of Sciences , Kalpana Mujoo, Ph.D., along with other researchers in Murad's lab, demonstrated the role nitric oxide and soluble guanylyl cyclase (nitric oxide receptor) play in the conversion of mouse and human embryonic stem cells into heart cells. Nitric oxide and cyclic guanosine monophosphate (cGMP) were shown to influence the differentiation of embryonic cells into myocardial cells. Similar strategy can be used to promote differentiation of stem cells into the lineages specific for the nervous system.

Rick A. Wetsel, Ph.D., professor and the William S. Kilroy Sr. Chair in Pulmonary Disease at the IMM, is leading a research program on the use of human embryonic stem cells to develop a transplantable source of lung cells that could be used to treat lung diseases such as acute respiratory distress syndrome and emphysema. Wetsel's team is also using these cells for gene therapy for inherited genetic defects affecting the lungs including cystic fibrosis and surfactant protein deficiency. His colleagues include Dachun Wang, M.D., (instructor) and Eva Zsigmond, Ph.D., (assistant professor and associate director of the Laboratory for Developmental Biology).

In a Proceedings of the National Academy of Sciences paper in 2007, Wetsel reported his laboratory was the first to generate a pure population of lung cells that could be used for lung transplantation. Subsequent studies using lung cells derived from embryonic stem cells have shown to be very promising in repairing tissue damaged by acute lung injury in mice.

Made possible by support from the Clive and Nancy Runnells Program in Embryonic Stem Cell Research, Wetsel, Wang and Zsigmond are also working on the development of “universal donor” stem cell lines that would not be rejected by a patient's immune system. Moreover, these lines have not been grown on mouse feeder layers and could be used for clinical applications.

Adult stem cell research

A past president of the International Society for Stem Cell Research (ISSCR) and current IMM professor, Paul J. Simmons, Ph.D. has performed pioneering studies with two populations of stem cells found in bone marrow. The first population is termed mesenchymal stem cells (MSC), a type of adult stem cell that can develop into bone, cartilage and fat tissue. The second population is called hematopoietic stem cells (HSC), which are responsible for the formation of the wide range of cell types in the blood.

In addition to studies of the basic biological properties of these two populations, a major focus of his laboratory in the Centre for Stem Cell Research at the IMM is to exploit the therapeutic potential of MSC and HSC. The Centre for Stem Cell Research is involved in the use of mesenchymal stem cells to treat non-union fractures in Australia. Following the success of clinical trials, they could be used in orthopaedic applications in the Texas Medical Center. The MSC population, previously defined by Simmons, is already being examined at the Texas Heart Institute at St. Luke's Episcopal Hospital to treat myocardial infarction and in pre-clinical studies to examine their utility as a cell therapy for the treatment of spinal cord injury.

Simmons' Centre, in collaboration with The University of Texas M. D. Anderson Cancer Center, is studying the use of MSCs as a way to improve the safety of cord blood transplantation.

Yong-Jian Geng, M.D., Ph.D., professor of medicine and director of the Center for Cardiovascular Biology and Atherosclerosis Research at The University of Texas Medical School at Houston, and James Willerson, M.D., professor and Edward Randall III Chair in Internal Medicine, are conducting adult stem cell research for wound healing and heart failure with grants from the U.S. Department of Defense. Supported by NIH, they also are studying death and regeneration of vascular stem cells in atherosclerosis and aortic aneurysms and stem cell therapy for animal myocardial infarction. Approved by the FDA, their clinical trial on treating chronic heart failure with stem cells is supported by the NIH. Geng also is a co-investigator on a study using stem cells for animals with atherosclerosis and diabetes, which is supported by the American Heart Association.

Principal investigator Charles Cox, M.D., professor of pediatric surgery at the UT Medical School, is leading a unique clinical trial that will gauge the safety and potential of treating children who have just suffered traumatic brain injury with stem cells derived from their own bone marrow. Approved by the FDA and the university's Committee for the Protection of Human Subjects (CPHS), the clinical trial is building on animal-model research indicating that bone-marrow derived stem cells can migrate to an injured area of the brain and support brain repair. Ten patients were recruited between 2005 and 2008. The study will be completed this summer.

Sean Savitz, M.D., assistant professor of neurology at the UT Medical School, has begun a similar Phase I safety study using bone marrow stem cells in acute stroke patients admitted to the emergency center at Memorial Hermann – Texas Medical Center. The study uses the patients' own bone marrow and is funded with a $130,000 NIH pilot grant. Enrollment of 10 patients is underway.

Ali E. Denktas, M.D, assistant professor of internal medicine in the Division of Cardiology, is studying endothelial progenitor cells, stem cells that circulate in the blood. He is investigating their ability to be used as a marker for outcomes in sudden cardiac death and acute myocardial infarction patients. He also is researching the interaction between these stem cells and cardiac risk factors, and is lead investigator for a clinical trial using mesenchymal cells for the treatment of myocardial infarction.

Shiwei Cai, D.D.S., assistant professor of endodontics at The University of Texas Dental Branch at Houston, is seeking to use stem cells derived from dental pulp within a patient's baby teeth or wisdom teeth for “tooth regeneration” as the answer to teeth dying after root canals. The research team's goal is to find the universal stem cell to use in tooth cloning and future therapies for gum disease, bone loss and other conditions.

Ka Bian, MD, Ph.D., a scientist in Murad's lab, is trying to determine if cancer stem cells could be one of the main factors contributing to the extended survival and resilience of malignant brain tumors. Promising molecular targets for treatment of human glioma have been defined.