Hematopoietic stem cells and solid organ transplantation

Abstract

Solid organ transplantation provides life saving therapy for patients with end stage organ disease. In order that the transplanted organ 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.

Graft‐Versus‐Tumor Effect in Major Histocompatibility Complex–Mismatched Mouse Liver Transplantation

“…The development of nonmyeloablative conditioning regimens before allo HSCT has allowed this therapy to be used in elderly and disabled patients . This allogeneic GVT effect has been observed in a number of patients with renal, breast, colorectal, ovarian, and pancreatic cancer treated with allo HSCT . In general, the tumor response is associated with the development of acute and chronic GVT disease …”

“…(23) This allogeneic GVT effect has been observed in a number of patients with renal, breast, colorectal, ovarian, and pancreatic cancer treated with allo HSCT. (20,24) In general, the tumor response is associated with the development of acute and chronic GVT disease. (25,26) The liver is rich in immune cells as well and has unique immune characteristics.…”

Successful long‐term outcome after combined hematopoietic stem cell transplantation and small bowel transplantation: A case report and review of the literature

“…We postulate that timing the HSCT well before SOT may reduce the likelihood of GVHD as the HSCT is likely to have decreased effector T cells, and new cells are more likely to tolerate different tissues. Indeed, combined marrow and organ transplants in animal models have been shown not to need chronic immunosuppression …”

Progress in Liver Transplant Tolerance and Tolerance-Inducing Cellular Therapies

“…When donor bone marrow is injected into the host that has undergone lymphoablation, such as total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG), HSCs are implanted into the recipient bone marrow and thymus for differentiation, and the host immune system is repopulated with various lymphocyte cells from the donor following by the immunoreconstitution. The presence of donor progenitor cells in the thymus leads to the apoptosis of T cells that recognize the donor antigen expressed by the transplanted organ itself without developing and donor-reactive T cells would undergo clonal deletion, so the host can tolerate the allograft ( 67 ). The coexistence of host and donor hematopoietic cells is called chimera, and it is this chimera state in the host that drives central tolerance.…”