Department of Biochemistry
School of Medicine & Biomedical Sciences
Faculty
Department of Biochemistry
School
of Medicine & Biomedical Sciences
Faculty
TE-CHUNG LEE, Ph.D.
Associate Professor
Email: chunglee@buffalo.edu
Bone Marrow Stem Cell Biology and Therapeutics
Bone marrow provides the structural and functional environment for the generation of hematopoietic stem cells as well as non-hematopoietic stem cells, which are often described as marrow stromal or mesenchymal stem cells (MSCs). MSCs can be readily isolated and amplified from a small aspirate of bone marrow. Ex vivo expanded MSCs retain their multi-lineage potentials, and typically express multiple surface markers such as CD29, CD44, CD73, CD90, CD105, and CD106. MSCs produce a plethora of trophic factors known to promote tissue regeneration. We have been studying the biology and genetic engineering of MSCs for therapeutic applications. The growth, differentiation, and trophic factor secretion potentials of MSCs are strongly influenced by multiple signaling pathways. A thorough understanding of these regulatory processes can lead to optimized therapeutic strategies for tissue regeneration. We have explored the immunomodulatory property of MSCs in our cell transplantation studies, and found that large quantities of human and porcine MSCs can be implanted in immunocompetent pigs, mice, and hamsters without inflaming the host immune system. These studies show that MSCs improve cardiac function in the porcine myocardial ischemia and hamster heart failure models. Implanted MSCs promote tissue regeneration by recruiting bone marrow progenitor cells and activating local host stem cell niches. These attributes of MSCs are mediated by inter-tissue cross-talk mechanisms involving signaling molecules such as JAK/STAT3, integrins, VEGF receptors, and Wnt/b-catenin. Our long-term goal is to generate clinically relevant stem cell information that may be used to achieve robust therapeutic effects for a broad spectrum of human diseases and lower the cost of future stem cell therapy.
Recent Publications:
Shabbir A, Zisa D, Suzuki G, and Lee T. Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a non-invasive therapeutic regimen. Am J Physiol 296:H1888-H1897, 2009
Shabbir A, Zisa D, Leiker M, Johnston C, Lin H, and Lee T. Muscular dystrophy therapy by non-autologous mesenchymal stem cells: muscle regeneration without immunosuppression and inflammation. Transplantation 87:1275-1282, 2009Missihoun C, Zisa D, Shabbir A, Lin H, and Lee T. Myocardial oxidative stress, osteogenic phenotype, and energy metabolism are differentially involved in the initiation and early progression of d-sarcoglycan-null cardiomyopathy. Mol Cell Biochem 321:45-52, (2009)
Leiker M, Suzuki G, Iyer VS, Canty JM Jr., and Lee T. Assessment of a nuclear affinity labeling method for tracking implanted mesenchymal stem cells. Cell Transplantation 17:911-922, (2008)
Lin H, Shabbir A, Molnar M, Yang J, Marion S, Canty JM Jr., and Lee T. Adenoviral expression of vascular endothelial growth factor splice variants differentially regulates bone marrow-derived mesenchymal stem cells. J Cell Physiol 216:458-468, (2008)
Lehning P, Lee T, Fallavollita JA, Canty JM Jr., and Suzuki G. Intracoronary administration of AdvFGF-5 (fibroblast growth factor-5) ameliorates left ventricular dysfunction and prevents myocyte loss in swine with developing collaterals and ischemic cardiomyopathy. Circulation 116:I71-I76, (2007)
Lin H, Shabbir A, Molnar M and Lee T. Stem cell regulatory function mediated by expression of a novel mouse Oct4 pseudogene. Biochem Biophys Res Comm 355:111-116, 2007
Lin H, McGrath J, Wang P, and Lee T. Cellular toxicity induced by SRF-mediated transcriptional squelching. Toxicol Sci 96:83-91, (2007)
Wang X, Hu Q, Mansoor A, Lee J, Wang Z, Lee T, From AH and Zhang J. Bioenergetic and functional consequences of Stem Cell Based VEGF delivery in pressure-overloaded swine hearts. Am J Physiol (Heart Circ Physiol) 290:H1393-1405, (2006)
Suzuki G, Lee T, Fallavollita JA and Canty JM Jr. Adenoviral gene transfer of FGF-5 to hibernating myocardium improves function and stimulates myocytes to hypertrophy and reenter the cell cycle. Circ Res 96:767-775, 2005
Vacanti V, Kong E, Suzuki G, Sato K, Canty JM Jr, and Lee T. Phenotypic changes of adult porcine mesenchymal stem cells induced by prolonged passaging in culture. J Cell Physiol 205, 194-201, (2005)