Hematopoietic stem cell infusion/transplantation for induction of allograft tolerance

Abstract

Purpose of review This review updates the current status of basic, preclinical, and clinical research on donor hematopoietic stem cell infusion for allograft tolerance induction. Recent findings Recent basic studies in mice provide evidence of significant involvement of both central deletional and peripheral regulatory mechanisms in induction and maintenance of allograft tolerance effected through a mixed chimerism approach with donor hematopoietic stem cell infusion. The presence of heterologous memory T cells in primates hampers the induction of persistent chimerism. Durable mixed chimerism, however, now has been recently induced in inbred major histocompatibility complex-mismatched swine, resulting in tolerance of vascularized composite tissue allografts. In clinical transplantation, allograft tolerance has been achieved in human leukocyte antigen-mismatched kidney transplantation after the induction of transient mixed chimerism or persistent full donor chimerism. Summary Tolerance induction in clinical kidney transplantation has been achieved by donor hematopoietic stem cell infusion. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, as well as to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications.

Combined Anti‐CD154/CTLA4Ig Costimulation Blockade‐Based Therapy Induces Donor‐Specific Tolerance to Vascularized Osteomyocutaneous Allografts

“…The level and duration of hematopoietic chimerism required to achieve transplantation tolerance have not been completely elucidated. Equally, the relative contributions of central thymic deletion versus peripheral regulatory mechanisms of host alloreactive lymphocytes to the initiation and maintenance of immune tolerance remain to be determined . Longitudinal monitoring of peripheral chimerism, in the current study, revealed that despite a viable intragraft BM component, chimerism levels were steadily declining over time.…”

Notch-Expanded Murine Hematopoietic Stem and Progenitor Cells Mitigate Death from Lethal Radiation and Convey Immune Tolerance in Mismatched Recipients

“…Allogeneic HCT promotes donor‐specific immune tolerance and subsequently decreases the risk for acute and chronic graft rejection in recipients of solid organ transplants . Successful conveyance of allograft immune tolerance in the nonmyeloablative HSCT setting with persistent mixed chimerism and complete withdrawal of immunosuppressive drugs has already been shown in renal transplant recipients .…”

Allogeneic transplantation of hematopoietic stem cells and solid organ in the same patient: an update

“…Some groups have worked for many years to develop methods to achieve tolerance to solid organ transplants by hematopoietic cell transplantation, aiming at mixed or complete chimerism [7,8,14,19,[22][23][24]28,29]. The aim would be to avoid life-long immunosuppressive treatment with its adverse effects.…”