Abstract
Cell-based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types are being tested as possible routes to tolerance induction, in the absence of donor-derived stem cells. Early data with each of these cell types have been encouraging. However, the induction regimen capable of achieving consistent tolerance, while avoiding unwanted sided effects, and which is scalable to the human patient, has yet to be identified. Here, we present the status of investigations of various tolerogenic cell types and the mechanistic rationale for their use in tolerance induction protocols.
Highlights
Cell-based therapies lie at the root of transplantation tolerance induction protocols
We will review some of the cell types, which have demonstrated tolerogenicity in both experimental and in preclinical models, focusing on the potential for tolerance induction in man
Adapted from bone-marrow transplantation efforts to reduce the rate of bone-marrow graft failure following haplo-identical transplantation, mesenchymal stem cells may be capable of tolerance induction [22, 23]
Summary
Cell-based therapies lie at the root of transplantation tolerance induction protocols. This, and other, observation prompted Peter Medawar to explore the possibility that donor chimerism would allow for acceptance of skin grafts from the same donor through which chimerism was established [2, 3] These findings, which led to the Noble Prize in 1960, were exploited by Dr David Sachs [4] and Dr Sam Strober [5] such that preclinical models [6] for tolerance to solid organ transplants could be developed [7,8,9]. Since the completion of Medawar’s experiments, investigators have sought to identify the cell populations responsible for tolerance induction. Even today, these cell types and their mechanisms remain elusive. We will review some of the cell types, which have demonstrated tolerogenicity in both experimental and in preclinical models, focusing on the potential for tolerance induction in man
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