Center for Transplantation Sciences
Explore This Lab
Historically, there have been two major problems in the field of organ transplantation: chronic immunosuppression and donor organ shortage.
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.
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 have just initiated a new clinical trial with the revised regimen aiming at inducing tolerance more efficiently and safely. We are also attempting to extend our approach to deceased organ transplantation (kidney, heart and lung transplantation) using a newly developed “delayed tolerance” conditioning protocol.
Another major problem is organ shortage. Currently, over 108,000 individuals need an organ, but fewer than 40,000 transplants are performed every year in the U.S. To address this unmet health care need, we are investigating the use of porcine organs for human transplantation. With recent advances in genetic modification technology, we have now achieved an over 600-day kidney xenograft survival rate in nonhuman primates with only one or two immunosuppressive medications.
We expect to have the first human clinical trial launch in a couple of years.
A. Benedict Cosimi, MD
Senior Investigator/Co-Head, Cosimi/Kawai Laboratory, Center for Transplantation Sciences (CTS)
Chief Emeritus, Division of Transplantation, Massachusetts General Hospital
Claude E. Welch Distinguished Professor of Surgery, Harvard Medical School
Tatsuo Kawai, MD, PhD
Senior Investigator/Co-Head, Cosimi/Kawai Laboratory (CTS)
A. Benedict Cosimi Chair in Transplant Surgery, Massachusetts General Hospital
Professor of Surgery, Harvard Medical School
Postdoctoral Research Fellows
Ahmad Karadagi, MD, PhD
Toshihide Tomosugi, MD
Ryo Otsuka, PhD
Abbas Dehnadi, DMD
Kerry Crisalli, RN
Grace Lassiter, MD (St. Elizabeth Hospital), Takayuki Hirose, MD (Hokkaido Univ.), Tetsu Oura, MD (Hokkaido Univ.), Kiyohiko Hotta, MD (Hokkaido Univ.), Masatoshi Matsunami, MD (Kameda General Hospital), 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 CTS is leading the following research projects:
Bcl-2 inhibition to induce hematopoietic chimerism without myelosuppression
Clinical trial for tolerance induction in HLA mismatched kidney transplant recipients
Transplantation of kidney xenograft
Studies to control ischemia/reperfusion injury
Center for Transplantation Sciences
The Center for Transplantation Sciences (CTS) at Massachusetts General Hospital conducts critical research to increase the success rates of transplantation and meet the growing demand for organ and bone marrow transplantation.