Regenerative Medicine and Stem Cells

Several faculty affiliated with the Barshop Institute are working on research concerning regenerative medicine and stem cells. Studies are aimed at understanding changes in stem cells in the body during aging. Other research is aimed at developing new methods to use stem cells for healing organs and tissues that have been damaged by aging and age-related diseases.

Basic Biology of Stem Cells in Aging and Cancer. The lab of LuZhe Sun, PhD Professor of Cell Systems and Anatomy is studying the regulatory role of an aging microenvironment on normal and cancer-forming stem cells in the mammary gland. See Figure 1 for details. The lab of Christi Walter, PhD Professor and Chair of Cell Systems and Anatomy is studying the aging of testicular stem cells.

Neural Stem Cells in Aging. The lab of Erzsebet Kokovay, PhD Professor of Cell Systems and Anatomy is studying the changes in neural stem cells that occur with age. See Figure 2 for details.

Induced Pluripotent Stem Cells for Age-Related Diseases. Human cells with the properties of embryonic stem cells can be derived from skin fibroblasts by reprogramming. These cells are termed “induced pluripotent stem cells” (iPS cells) and their creation is thought by many scientists to be a major advance in terms of ethics, medical therapy and basic science. Although iPS cells may be the starting point for future cell therapy, the major issues that face scientists now are the same as was previously raised for embryonic stem cells: how to cause them to differentiate into useful cell types (e.g. brain, heart, insulin-secreting and so on) and how to test whether these cells can be safely used in cell therapy. Peter Hornsby, PhD Professor of Cellular and Integrative Physiology is an expert on the processes for deriving iPS cells and has written several overviews of their future potential use for therapy of age-related diseases. John McCarrey, PhD Professor of Biology at UTSA, is developing the baboon as a model system for testing stem cell-based therapeutic applications.

Mesenchymal Stem Cells in Aging and Cancer. Mesenchymal stem cells are pluripotent cells with great promise for regenerative medicine that are found in all tissues of the body; fat and bone marrow are good sources of these cells. Although they hold great promise they also are capable of stimulating the growth of cancer cells. The lab of Xiao-Dong Chen, MD, PhD Professor of Restorative Dentistry is characterizing the aging of human mesenchymal stem cells.

Stem Cell Therapy for Neurodegenerative Diseases. The lab of Senlin Li, MD Professor of Medicine is using a novel macrophage-delivered therapy for Parkinson’s disease. In addition, in conjunction with Robert Clark, MD Professor of Medicine, experiments in mice have shown that transplantation of hematopoietic stem cells can extend lifespan. The lab of Marcel Daadi, PhD Adjunct Associate Professor of Cell Systems and Anatomy is developing therapeutic neural stem cell lines for clinical use in stroke, Parkinson’s disease and other diseases and injuries.

Figure 1
Stem cell aging in the mouse mammary gland. (a and b) Gene set enrichment analysis is used to discover the differences in genes that are expressed in the young (4-6 mon.) and old (30-32 mon.) mouse mammary gland. Two sets (from Dr Sun's lab and that of Lim et al., 2010) of luminal signature genes were analyzed and indicated as black bars in the plots. The luminal cell signature genes were significantly enriched in the old basal cells, and no significant enrichment was seen in young or old luminal cells. (c-j) Immunostaining of representative mammary ducts from old (26-31 mon., n = 6) C57BL6/J mice showing that basal cells were CD49fhi, SMA+ and K8- in the majority normal (c, e) and hyperplastic ducts (d, f), but the presence of CD49fhi luminal cells (K8+, SMA-) in a few hyperplastic lesions (g-j). Scale bars, 10 μm. Images courtesy of Dr. Sun.
Figure 2
Organization of the vascular subventricular zone (V-SVZ), one of the locations of neural stem cells in the brain. A) Diagram of the V-SVZ niche in the mouse brain. The niche is a complex environment with several cell types playing various roles. Key elements are the blood vessels and the microglia. In aging, changes in the activity of the neural stem cells depend on changes in the blood supply to the niche and on changes in the activity of the microglia. B) The blood vessels appear green and dividing cells appear red in this fluorescence microscope image. C) The microglia appear purple in this image. Images courtesy of Dr. Kokovay.