Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: The long road to tolerance

J. Leventhal, J. Miller, M. Abecassis, D. J. Tollerud, S. T. Ildstad*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The immunoregulatory properties of hematopoietic stem cells (HSCs) have been recognized for more than 60 years, beginning in 1945, when Owen reported that genetically disparate freemartin cattle sharing a common placenta were red blood cell chimeras. In 1953, Billingham, Brent, and Medawar demonstrated that murine neonatal chimeras prepared by infusion of donor-derived hematopoietic cells exhibited donor-specific tolerance to skin allografts. Various approaches using HSCs in organ transplantation have gradually brought closer to reality the dream of inducing donor-specific tolerance in organ transplant recipients. Several hurdles needed to be overcome, especially the risk of graft-versus-host disease (GVHD), the toxicity of ablative conditioning, and the need for close donor-recipient matching. For wide acceptance, HSC therapy must be safe and reproducible in mismatched donor-recipient combinations. Discoveries in other disciplines have often unexpectedly and synergistically contributed to progress in this area. This review presents a historic perspective of the quest for tolerance in organ transplantation, highlighting current clinical approaches.

Original languageEnglish (US)
Pages (from-to)36-45
Number of pages10
JournalClinical pharmacology and therapeutics
Volume93
Issue number1
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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