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Yuanyuan Zhang, MD, PhD

Yuanyuan Zhang, M.D., Ph.D., Assistant Professor

Dr. Zhang received his M.S. and M.D. at Jiangxi Medical College in China. He completed his residency in urology and renal transplantation at the same medical institution, and then acted as a certified urologist in China. Following this, he completed a two-year research fellowship awarded by the international society of nephrology and trained in the Department of Urology/Nephrology at Christchurch Hospital in New Zealand. He earned the Doctorat EN Medecine (Ph.D. equivalent in the US) at the University of Lausanne in Switzerland in 2001. He completed postdoctorial training and became an assistant professor at the University of Oklahoma. Dr. Zhang joined the Institute for Regenerative Medicine in January 2006.
SYNOPSIS OF AREA OF INTEREST: Dr. Zhang's research interests include mesenchymal stem cells, biological scaffolds, cell therapy and tissue engineering for urology and andrology applications, enhanced 3D cell culture for drug development.

DETAILED AREA OF INTEREST: The current approach to urological tissue engineering involves obtaining cells from a patient’s urinary tract, growing these cells on a biodegradable scaffold in a bioreactor, and then transplanting the cell-scaffold construct back into the patient in order to replace defective organs or tissue. However, in certain clinical situations such as neuropathic bladder or bladder cancer, normal tissue or cells are not available for use in tissue engineering applications. Bone marrow-derived mesenchymal stem and progenitor cells have the capacity to differentiate into various types of cells and might be an alternative cell source for urologic tissue engineering for these patients. We have demonstrated that bone marrow stromal cells can have similar cell proliferation rates, histological appearance and contractile phenotype as bladder smooth muscle cells in culture. In addition, bone marrow stromal cells seeded onto scaffolds made from small intestinal submucosa enhanced bladder regeneration in vivo. The goal of our current research is to induce bone marrow stem cells to differentiate into bladder smooth muscle cells in order to improve bladder function and regeneration. To promote growth and differentiation of bone marrow stromal cells, we use a co-culture technique and mechanical stress systems to induce the adult stem cells to differentiate into smooth muscle cells. Using an animal model of bladder reconstruction and gene transfection approaches (transfection of reporter genes such as Lac-Z or enhanced green fluorescent protein) to visualize the implanted cells, we are studying the in vivo survival of bone marrow stem and progenitor cells and their impact on the bladder function and regeneration. We are also exploring the roles of several growth factors in angiogenesis and differentiation of bone marrow stem cells into different types of cells needed for the bladder tissue regeneration process. 

Recently, we have determined that multipotent stem cells can be routinely isolated from normal human urine. These urine derived stem cells (USC) possess the biological properties characteristic of mesenchymal stem cells (MSC), including clonogenicity, the ability to expand into large populations, and the capacity to differentiate into a number of different cell types. Upon induction with appropriate media, these cells can differentiate into cells of the osteogenic, chondrogenic, adipogenic and myogenic lineages. Their differentiation into bladder cells, smooth muscle cells and urothelial cells is particularly efficient. Furthermore, USC can be obtained from both voided urine and urine obtained from the upper urinary tract. USC from both sources are similar in terms of the cellular characteristics noted above. USC provide a promising alternative cell source for various cell therapy and tissue engineering applications relevant to urology, such as reconstruction of the bladder and urethra and cell-based therapy for stress urinary incontinence, but one day they could also be used in other surgical fields to repair damaged or defective tissues outside the urinary tract.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      




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