The thymus is a rich source of regulatory T cells and plays a role in self-tolerance. Therefore, transplantation of a vascularized donor thymus may facilitate the induction of tolerance in recipients of a cotransplanted heart allograft. To investigate this hypothesis, we developed a new technique to procure the heart and thymus en bloc from juvenile donors and transplant the composite allograft into thymectomized recipients.
View Article and Find Full Text PDFHematopoietic stem cell transplantation (HSCT) has many potential applications beyond current standard indications, including treatment of autoimmune disease, gene therapy, and transplant tolerance induction. However, severe myelosuppression and other toxicities after myeloablative conditioning regimens have hampered wider clinical use. To achieve donor hematopoietic stem cell (HSC) engraftment, it appears essential to establish niches for the donor HSCs by depleting the host HSCs.
View Article and Find Full Text PDFBackground: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts.
Methods: Five cynomolgus macaques underwent left orthotopic lung transplantation.
The lack of a reliable and reproducible large animal tumor model for the study of hemolymphatic malignancies limits the ability to explore the underlying pathophysiology and testing of novel therapies. The goal of this study was to develop an aggressive, trackable swine tumor cell line in mice for adoptive transfer into MHC matched swine. Two tumor cell lines, post-transplant lymphoproliferative disease (PTLD) 13271 and chronic myelogenous leukemia (CML) 14736, were previously established from the Massachusetts General Hospital (MGH) miniature swine herd.
View Article and Find Full Text PDFThymic involution is associated with age-related changes of the immune system. Utilizing our innovative technique of transplantation of a thymus as an isolated vascularized graft in MHC-inbred miniature swine, we have previously demonstrated that aged thymi are rejuvenated after transplantation into juvenile swine. Here we have studied the role of insulin-like growth factor (IGF) and forkhead-box protein-N1 (FOXN1) as well as bone marrow (BM) in thymic rejuvenation and involution.
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