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

Abstract:

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.

authors

Cetrulo CL Jr,Drijkoningen T,Sachs DH

doi

10.1097/MOT.0000000000000248

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

602-7

issue

6

eissn

1087-2418

issn

1531-7013

pii

00075200-201512000-00004

journal_volume

20

pub_type

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