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Research at Mass General
The Cosimi/Kawai Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital focuses on allograft tolerance induction (the successful transplantation of an organ or tissue without immunosuppression) in nonhuman primates and humans, with the goal of developing safe and reliable tolerance-inducing regimens for clinical transplantation.
Short-term results following organ transplantation have been significantly improved by the use of increasingly effective immunosuppressive agents. However, their chronic use results in significant morbidity, especially from an increased incidence of cardiovascular disease, infection, malignancies, de novo diabetes and other metabolic disorders.
Additionally, the effects of current therapeutic protocols to regulate the immune system often do not prevent the development of chronic rejection, despite their administration being pushed to toxic levels.
Because of this, induction of tolerance, defined as the absence of destructive immune responses to a transplanted tissue without ongoing immunosuppressive therapy, remains the ultimate goal of organ transplantation.
Since the 1950s, numerous strategies for induction of tolerance have been developed in small animal models, but none of these studies has ever successfully translated to large animal models until our laboratory reported a nonmyeloablative conditioning regimen that consistently induced renal allograft tolerance in nonhuman primates (NHP) via a mixed chimerism approach, a state induced by bone marrow transplantation where host and donor cells exist without any rejection (Kawai, T et al. Transplantation 1995).
Our laboratory subsequently applied our approach in human leukocyte antigen (HLA)-mismatched kidney transplantation, and renal allograft tolerance was achieved with the longest kidney allograft survival now exceeding 12 years without any immunosuppression. This is a seminal translation of an observation, first made in mice to a preclinical NHP model, then to the first reproducibly successful induction of tolerance of renal allografts in humans that was reported in the New England Journal of Medicine in 2008 and 2013.
We are now attempting to extend our approach to deceased organ transplantation (kidney, liver and pancreatic islets) using a newly developed “delayed tolerance” conditioning protocol.
A. Benedict Cosimi, MD
Senior Investigator/Co-Head, Cosimi/Kawai Laboratory, Center for Transplantation Sciences (CTS) Chief Emeritus, Division of Transplantation, Massachusetts General HospitalClaude E. Welch Distinguished Professor of Surgery, Harvard Medical School
Tatsuo Kawai, MD, PhDSenior Investigator/Co-Head, Cosimi/Kawai Laboratory (CTS)A. Benedict Cosimi Chair in Transplant Surgery, Massachusetts General HospitalProfessor of Surgery, Harvard Medical School
Abbas Dehnadi, DVMKiyohiko Hotta, MDTetsu Oura, MD
Kerry Crisalli, RN
Svjetlan Boskovic, MD, Ognjenka Nadazdin, MD, Yohei Yamada, MD (Keio University), Aki Aoyama, MD (Kyoto University), Soyoung Lee, MD (University of Pittsburgh Medical Center), Derek Klarin, MD (Mass General), Toru Murakami, MD (Tokyo Women’s Medical University), Takanori Ochiai, MD (Tokyo Medical and Dental University), John Mercer, MD, Ichiro Koyama, MD (Tokyo Women’s Medical University), Nahel Elias, MD (Mass General), Hiroshi Sogawa, MD (University of Pittsburgh Medical Center), Gregory Abrahamian, MD (University of Texas)
The Cosimi/Kawai Laboratory in the Center for Transplantation Sciences is leading the following research projects:
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