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Mixed chimerism and transplantation tolerance.

A Benedict Cosimi1, David H Sachs

  • 1Transplantation Unit of the General Surgical Service, and the Transplantation Biology Research Center, Massachusetts General Hospital, and the Department of Surgery, Harvard Medical School, Boston, USA.

Transplantation
|April 13, 2004
PubMed
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Mixed hematopoietic chimerism induces transplant tolerance. This strategy, refined in mice and monkeys, shows promising early results in renal transplant patients, even with mismatched donors.

Area of Science:

  • Immunology
  • Transplantation Science
  • Regenerative Medicine

Background:

  • Mixed hematopoietic chimerism is a strategy to induce transplantation tolerance.
  • This approach has been validated in preclinical models, including mice and non-human primates.
  • Previous research has focused on establishing tolerance to various tissues and organs.

Purpose of the Study:

  • To review the evolution of mixed hematopoietic chimerism from preclinical studies to clinical applications.
  • To present current clinical experience with two therapeutic protocols for renal transplant patients.
  • To evaluate the efficacy of mixed hematopoietic chimerism in inducing tolerance in kidney transplant recipients.

Main Methods:

  • Preclinical studies in mice and cynomolgus monkeys.

Related Experiment Videos

  • Development and application of modified protocols for human clinical trials.
  • Two distinct therapeutic protocols for renal transplant patients: one with HLA-matched sibling donors and one with HLA-mismatched donors.
  • Monitoring of tolerance induction and patient outcomes.

    • Main Results:

    • Encouraging early results in renal transplant patients undergoing mixed hematopoietic chimerism protocols.
    • Successful induction of tolerance observed in both HLA-matched and HLA-mismatched donor scenarios.
    • The strategy has been successfully translated from animal models to human patients.

    Conclusions:

    • Mixed hematopoietic chimerism is a viable strategy for inducing transplantation tolerance in humans.
    • Early clinical data suggest this approach is effective for renal transplant patients.
    • Further studies are warranted to confirm long-term outcomes and optimize protocols.