Although many diabetic patients in renal failure, especially children, have potential donors willing to provide both a kidney and islets, the quantity of islets necessary to achieve insulin independence hampers successful islet Tx by partial pancreatectomy from living donors. Project 2 is designed toward developing a tolerance-inducing strategy for curative treatment of end-stage diabetic nephropathy using living donor composite Islet-Kidney (IK) transplantation (Tx). We have previously demonstrated that the strategy of transplanting pre-vascularized islets as part of IKs in large animal models is successful, using far fewer islets than are required for Tx of free, non-vascularized islets. Both renal and islet function were restored by IK Tx across fully allogeneic barriers in nephrectomized diabetic baboons using a clinically relevant immunosuppression protocol. More recently, our preliminary data have shown the successful induction of tolerance of IKs in rhesus monkeys treated with hematopoietic cell Tx in a

Public Health Relevance

Although many diabetic patients in renal failure, especially children, have potential donors who would be willing to donate both a kidney and a portion of their pancreas, the quantity of islets necessary to achieve insulin independence is currently far greater than is obtainable from the amount of pancreas that can safely be removed from the living donor. This research proposal is directed towards an approach that combines islets and a kidney into a composite

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-MFH-I (M1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Dehnadi, Abbas; Benedict Cosimi, A; Neal Smith, Rex et al. (2017) Prophylactic orthosteric inhibition of leukocyte integrin CD11b/CD18 prevents long-term fibrotic kidney failure in cynomolgus monkeys. Nat Commun 8:13899
Pathiraja, V; Villani, V; Tasaki, M et al. (2017) Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys. Am J Transplant 17:91-102
Hotta, Kiyohiko; Aoyama, Akihiro; Oura, Tetsu et al. (2016) Induced regulatory T cells in allograft tolerance via transient mixed chimerism. JCI Insight 1:
Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan et al. (2016) Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation. Cell Transplant 25:1331-41
Granados, Jose M M; Benichou, Gilles; Kawai, Tatsuo (2015) Hematopoietic stem cell infusion/transplantation for induction of allograft tolerance. Curr Opin Organ Transplant 20:49-56
Tonsho, M; Lee, S; Aoyama, A et al. (2015) Tolerance of Lung Allografts Achieved in Nonhuman Primates via Mixed Hematopoietic Chimerism. Am J Transplant 15:2231-9
Yamada, Y; Nadazdin, O; Boskovic, S et al. (2015) Repeated Injections of IL-2 Break Renal Allograft Tolerance Induced via Mixed Hematopoietic Chimerism in Monkeys. Am J Transplant 15:3055-66
Oura, Tetsu; Hotta, Kiyohiko; Cosimi, A B et al. (2015) Transient mixed chimerism for allograft tolerance. Chimerism 6:21-6
Kant, Cavit D; Akiyama, Yoshinobu; Tanaka, Katsunori et al. (2015) Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues. J Immunol 194:1364-71
Wang, Ping; Schuetz, Christian; Vallabhajosyula, Prashanth et al. (2015) Monitoring of Allogeneic Islet Grafts in Nonhuman Primates Using MRI. Transplantation 99:1574-81

Showing the most recent 10 out of 44 publications