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Tolerance induction via mixed chimerism in vascularized composite allotransplantation: is it time for clinical application?

Cetrulo, Curtis L. Jra,b,c; Drijkoningen, Tessaa,b; Sachs, David H.a

Current Opinion in Organ Transplantation: December 2015 - Volume 20 - Issue 6 - p 602–607
doi: 10.1097/MOT.0000000000000248
COMPOSITE TISSUE TRANSPLANTATION: Edited by Emmanuel Morelon
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Purpose of review The present review summarizes current data on the induction of immunologic tolerance through mixed hematopoietic chimerism relevant to applying this approach to vascularized composite allotransplantation.

Recent findings Clinical allograft tolerance has been achieved recently for kidney transplants, using nonmyeloablative conditioning regimens and bone marrow transplantation from living donors. The mixed chimerism attained in these studies was either transient or durable, and both permitted tolerance of the renal allografts to be achieved across MHC-matched and MHC-mismatched barriers. In order to extend these protocols to deceased donor transplants across full MHC-mismatched combinations, as will be required for vascularized composite allografts (VCA), a delayed tolerance protocol has recently been developed, in which the donor bone marrow is given 4 months posttransplant. Recent primate studies of kidney transplants using this protocol have been successful and have demonstrated that strategies to abrogate memory T cells may be helpful.

Summary Induction of tolerance in renal allograft transplantation has been achieved clinically, via mixed chimerism protocols. Modifications of these protocols for transplants, which require use of deceased donors across full MHC mismatches, have shown promise in preclinical models. It is therefore appropriate to consider evaluation of these protocols in clinical trials for kidney transplants, and if successful, for VCA.

aVascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA

bDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

cTransplantation Biology Research Center Laboratories, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA

Correspondence to Curtis L. Cetrulo, Jr., MD, FACS, FAAP, Transplantation Biology Research Center Laboratories, Center for Transplantation Sciences, Harvard Medical School, Massachusetts General Hospital, MGH-East Building 149, 13th Street, Boston, MA 02129, USA. Tel: +1 617 726 4065; e-mail: ccetrulo@mgh.harvard.edu

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