Hematopoietic stem cells and solid organ transplantation

Abstract

Solid organ transplantation provides lifesaving therapy for patients with end stage organ disease. In order for the transplanted organ to survive, the recipient must take a lifelong cocktail of immunosuppressive medications that increase the risk for infections, malignancies and drug toxicities. Data from many animal studies have shown that recipients can be made tolerant of their transplanted organ by infusing stem cells, particularly hematopoietic stem cells, prior to the transplant. The animal data have been translated into humans and now several clinical trials have demonstrated that infusion of hematopoietic stem cells, along with specialized conditioning regimens, can permit solid organ allograft survival without immunosuppressive medications. This important therapeutic advance has been made possible by understanding the immunologic mechanisms by which stem cells modify the host immune system, although it must be cautioned that the conditioning regimens are often severe and associated with significant morbidity. This review discusses the role of hematopoietic stem cells in solid organ transplantation, provides an understanding of how these stem cells modify the host immune system and describes how newer information about adaptive and innate immunity might lead to improvements in the use of hematopoietic stem cells to induce tolerance to transplanted organs.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1. Schematic of mechanisms of HSC-induced tolerance

Donor HSCs home to the recipient thymus, where they integrate with recipient thymic cells and develop donor/recipient chimerism. The result of chimerism is that central tolerance mechanisms ensue allowing mature T cells to develop that can recognize donor antigens as self (tolerized). T cells that recognize donor antigens as foreign undergo apoptosis. T cells that escape to the periphery undergo peripheral tolerance mechanisms that result in either anergy (in the absence of costimulation) or apoptosis (in the presence of costimulation).