Research Centers

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Organ Transplantation Tolerance and Xenotransplantation Laboratory

The Organ Transplantation Tolerance and Xenotransplantation Laboratory in the Transplantation Biology Research Center works to develop strategies to induce tolerance across allogeneic and xenogeneic barriers to prevent rejection and relieve the current shortage of donor organs.

The Organ Transplantation Tolerance and Xenotransplantation Laboratory in the Transplantation Biology Research Center (TBRC) at Massachusetts General Hospital works to develop strategies to induce tolerance across both allogeneic and xenogeneic barriers in large animals with the ultimate goal of developing clinical tolerance induction protocols. Our current major projects include:

  • Tolerance of kidneys with calcineurin inhibitors
    We have developed a protocol involving 12 days of high-dose FK506, which facilitates the induction of thymic-dependent tolerance across fully-allogeneic barriers in major histocompatibility complex (MHC) inbred Mass General miniature swine. We are currently investigating mechanisms of peripheral tolerance focusing on the generation of T-regulatory cells. We have also documented linked suppression, the tolerance-inducing role of donor kidneys and adoptive transfer of tolerance in this large animal model
  • Importance of vascularization to induce tolerance
    We have demonstrated that vascularized thymic transplantation is a potential strategy to induce tolerance across both allogeneic and xenogeneic barriers. Using vascularized thymic lobetransplantation (VTL or thymokidneys), a technique developed by senior investigator Kazuhiko Yamada, MD, PhD, we have reported successful induction of tolerance of kidneys and hearts in miniature swine. Using this technique in conjunction with genetically modified GalT-KO pigs as donors, we have demonstrated the longest (>80 days) life-supporting porcine kidney xenograft survival in baboons. This innovative VTL transplantation technique has allowed us to study thymic rejuvenation and determine that it is predominantly controlled by extrinsic factors, which we are currently characterizing

Our lab has also extended this technique to islet transplantation. We have developed a method for transplantation of islets as a vascularized graft (islet-kidney). Life-supporting islet-kidneys from single donors achieved glucose regulation and maintained normal renal function in both pigs and non-human primates that were treated with tolerance-inducing regimens. This promising technique may be the basis for future clinical protocols for the treatment of diabetic nephropathy.

Principal Investigator
Kazuhiko Yamada, MD, PhD 
Senior Investigator/Head Organ Transplantation Tolerance and Xenotransplantation Laboratory,
Director, Surgical Research, TBRC
Associate Immunologist, Massachusetts General Hospital
Associate Professor of Surgery, Harvard Medical School
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Kazuhiko Yamada, MD, PhD, is the director of surgical research and head of the Organ Transplantation Tolerance and Xenotransplantation Laboratory in the Transplantation Biology Research Center (TBRC) at Massachusetts General Hospital. He obtained his medical degree and a Doctor of Philosophy from Nippon Medical School in Japan and is a board-certified urologist. He was a research associate at the TBRC, under the direct supervision of David H. Sachs, MD, in late 1993. In 1997, he became a group leader in the Large Animal Transplantation Section and an instructor of surgery at Harvard Medical School. In 2000, he was promoted to assistant professor of surgery at Harvard Medical School and assistant immunologist at Mass General. In 2004, he was promoted to associate professor of surgery at Harvard Medical School.

Dr. Yamada has performed more than 800 cases of allogeneic and xenogeneic kidney transplantation in large animal models and has published more than 130 articles in these fields. He is a member of the American Society of Transplantation, the Transplantation Society and a council member of Xenotransplantation, as well as several other transplantation, urology and dialysis societies in Japan.

Dr. Yamada's current research interests focus on finding new means for inducing tolerance to allogeneic and xenogeneic organ transplants.

Research Fellows
Akihiro Kawai, MD
Tatsu Tanabe, MD

Research Technologist
Shannon Pratts

Research Technician
Taylor Cormack
Teddy Harrington

The Organ Transplantation Tolerance and Xenotransplantation Laboratory leads the following projects:

  • Transplantation of islet-kidneys across allogeneic barriers in miniature swine and non-human primates to treat both renal failure and diabetes
  • Induction of tolerance across allogeneic and xenogeneic barriers using transplantation of vascularized thymic grafts, using either isolated vascularized graft (VTL) or thymokidneys
  • Development of optimal strategies to overcome current obstacles to life-supporting xeno-kidney grafts in order to achieve long-term graft acceptance
  • Elucidation of thymic-dependent, peripheral and central mechanisms of tolerance
  • Determining the mechanisms involved in thymic involution and rejuvenation in order to facilitate the clinical application of  VTLs and thymokidneys