The Cardiothoracic Transplantation Laboratory in the Center for Transplantation Sciences (CTS) at Massachusetts General Hospital is dedicated to:
The investigations in this laboratory utilize the MHC inbred miniature swine transplant system which is unique among large animal models of transplantation. Our focus on thoracic organs is based on the fact that the immune system responds more aggressively to heart and lung allografts than to other allografts such as kidney or liver. Experimental tolerance protocols that are successful in kidney or liver recipients are typically not as effective in heart or lung recipients. We believe that organ-specific research is critical to advancing the field of heart and lung transplantation.
Joren C. Madsen, MD, DPhil
Co-Director, Center for Transplantation Sciences (CTS)
Senior Investigator/Head, Cardiothoracic Transplantation Laboratory, CTS
Director, Massachusetts General Hospital Transplant Center
W. Gerald and Patricia R. Austen Distinguished Scholar in Cardiac Surgery
Professor of Surgery, Harvard Medical School
Deatrice Moore, Staff Assistant III to Dr. Madsen
Joren C. Madsen, MD, DPhil, received his Bachelor of Science from Brown University, his medical degree from the University of Massachusetts Medical School and a doctorate degree in immunology from Balliol College, Oxford University. Dr. Madsen completed a Massachusetts General Hospital surgical residency in 1990 and went on to train in cardiothoracic surgery at Mass General and Boston Children’s Hospital. He joined the professional staff of the Mass General Division of Cardiac Surgery in 1993. He was the surgical director of Cardiac Transplantation at Mass General between 1999 and 2006 and section chief of the Division of Cardiac Surgery between 2008 and 2011.
Currently, Dr. Madsen is Professor of Surgery at Harvard Medical School and the W. Gerald and Patricia R. Austen Distinguished Scholar in Cardiac Surgery at Mass General. He is the founding director of the Mass General Transplant Center and is co-director of the Transplantation Biology Research Center.
Dr. Madsen has served on the boards of the International Society of Heart and Lung Transplantation and the American Transplantation Society (AST), and on the editorial boards of Transplantation, American Journal of Transplantation and the Annals of Thoracic Surgery. He received the Fujisawa Basic Science Award from the AST in 2002 and in 2009 was the first surgeon to be elected president of the American Society of Transplantation.
James S. Allan, MD
Senior Investigator/Co-Head, Cardiothoracic Transplantation Laboratory, CTS
Associate Chief, Thoracic Surgery, North Shore Medical Center
Director, Surgical Intensive Care, North Shore Medical Center
Protocol Review Chair, Subcommittee for Research Animal Care, Massachusetts General Hospital
Assistant Professor of Surgery, Harvard Medical School
Lucia Madariaga, MD
PJ Spencer, MD
The Cardiothoracic Transplantation Laboratory leads the following research projects:
Heart allograft tolerance through mixed chimerism and kidney co-transplantation
Mixed chimerism, which is achieved by combining bone marrow and organ transplantation, is meant to trick the host immune system into recognizing the donor organ as self, inducing a state of transplant tolerance. This state makes chronic immunosuppression unnecessary, thereby eliminating the associated dangers, and has been achieved in recipients of kidney, but not heart, allografts. It is well known that kidney and liver allografts are tolerance-prone while heart and lung allografts are tolerance-resistant. We have taken advantage of the tolerogenicity of kidney allografts by co-transplanting a donor kidney with the heart allograft and have achieved long-term, stable tolerance of major histocompatibility complex (MHC) mismatched heart allografts for the first time in large animals. We are now using MHC inbred miniature swine to determine the kidney-specific cell or cell product responsible for mediating kidney induced cardiac allograft tolerance (KICAT). The ultimate goal is to utilize this renal cell or cell product instead of the donor kidney to achieve long-term, stable tolerance in patients transplanted with heart allografts alone.
Lung allograft tolerance in MHC inbred miniature swineOur laboratory is the first to have achieved long-term survival of lung allograft in fully mismatched swine without the need for ongoing immunosuppression. This has been accomplished using a short-term, high-dose course of tacrolimus, an immunosuppressive drug used in human transplant recipients. This state of tolerance is highly influenced by the state of inflammation and innate immune activation in the recipient at the time of transplantation. Current efforts in swine are directed toward understanding and mitigating the detrimental effects of proinflammatory cytokines and innate immune activation on tolerance induction using ex vivo lung perfusion.
Immunology of bioengineered organs
The concept of restoring tissue function by delivering functional cells, or engineered tissue constructs, introduced a new way of thinking for stem cell and development biologists, inspiring the goal to ultimately regenerate lost tissues. Organ engineering now takes that dream one step further to not only generate cells and tissues, but to generate whole organs that can be derived from a patient’s cells and transplanted like donor organs. The goal is to overcome donor organ shortage by being able to generate organs on demand and overcome the need for immunosuppression by using patient-derived cells. However, the immunogenicity of these constructs in unknown. In collaboration with Harald Ott, MD, we are bioengineering kidney grafts using decellularized porcine constructs reseeded with pig stem cells. They are being transplanted into MHC inbred miniature swine and the host immune response systematically analyzed.
Pig-to-primate lung xenotransplantation
We are collaborating with David H. Sachs, MD, and Kazuhiko Yamada, MD, in studies aimed at preventing hyperacute and delayed xenograft rejection, which should bring us closer to xenotransplantation in patient care. Donor lungs from genetically-manipulated miniature swine that do not express the target antigen for human natural antibodies (Gal-T KO pig) but do express relevant human proteins (i.e., CD47 and CD55) will be transplanted orthotopically into baboons treated with either standard triple-drug immunosuppression or a tolerance induction protocol comprising bone marrow transplantation (mixed chimerism).
MGH Hotline 12.3.10 Members of the MGH Transplant Center gathered in the Bigelow Amphitheater Nov. 17 to hear Joren Madsen, MD, DPhil, director of the MGH Transplant Center; Jay A. Fishman, MD, associate director of the center; and Debra J. Doroni, MBA, executive director of the center and the Department of Surgery, unveil the Transplant Center's new strategic plan.
After more than two decades of leading the MGH Transplantation Biology Research Center (TBRC), David H. Sachs, MD, is stepping down from his role as director.