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Experimental Study On Cardiac Xenotransplantation Tolerance Produced By Inducing Of The Mixed Chimerism Using BMC/BM-MSCs Combined With TGF-β1 Gene Transfer

Posted on:2007-08-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:J W HuFull Text:PDF
GTID:1104360185478778Subject:Thoracic and Cardiovascular Surgery
Abstract/Summary:PDF Full Text Request
Background:Heart allotransplantation has become a therapeutic option for patients with end-stage heart disease. Xenotransplantation is considered a promising, possible solution to the perennial lack of donor organs. Heart of phylogenetically-distant species are subject to more severe and irreversible rejection reaction than that in allograft. Advances in immunosuppressive drug have yielded improvement of transplantation; yet long-term survival recipient complications and graft loss continue to accompany chronic immunosuppression. Induction of tolerance may hold the key to improve transplant longevity and quality of life in recipient and increase the cost-effectiveness of transplant therapy at the same time. With further studies and developments of transplantation immunology, eliminating transplant rejection through inducing immune tolerance has become the main goal in organ transplantation.Transforming Growth Factor- beta 1 (TGF-β1), a known omnipresent cytokine, is a crucial potent protein of cellular growth and proliferation modulator and play an important role in organ-transplantation immunity. Chimerism is one of the most effective approaches of inducing donor-specific tolerance.In this study , we cloned rat TGF-β1 gene and constructed recombinant retrovirus vector carrying the target gene which could be expressed stably in guinea pig mesenchymal stem cells. We established a stable chimerism model with multiple intravenous injection of guinea pig bone marrow cells and mesenchymal stem cells in Xenogeneic Rats. Our study applies TGF-β1 retrovirus gene therapy combined with mixed chimerism to investigate whether it can induce the heart xenotransplantation immunotolerance in the rat. By this way, we investigated the application prospectives of TGF-β1 gene and chimerism in xenotransplantation Methods:1,To design and synthesize one pair of primers P1, P2 according to declared rat...
Keywords/Search Tags:Heart Xenotransplantaion, Immune Tolerance, Chimeras, Gene Therapy, TGF-β1, Mesenchymal Stem Cells
PDF Full Text Request
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