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Interrogating Individual Autoreactive Germinal Centers by Photoactivation in a Mixed Chimeric Model of Autoimmunity
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Induction of tolerance through mixed chimerism.

David H Sachs1, Tatsuo Kawai, Megan Sykes

  • 1Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129.

Cold Spring Harbor Perspectives in Medicine
|January 4, 2014
PubMed
Summary

Mixed chimerism, a mix of host and donor cells after stem cell transplants, is the only method for transplantation tolerance in large animals and clinics. This study compares its use across mice, pigs, monkeys, and humans.

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Area of Science:

  • Immunology
  • Transplantation Biology
  • Regenerative Medicine

Background:

  • Mixed chimerism involves donor and host cells in the lymphohematopoietic system post-allogeneic stem cell transplantation.
  • While successful in mice, mixed chimerism is the sole tolerance-inducing method advanced to large animals and clinical application.
  • This approach is typically achieved via bone marrow or mobilized peripheral blood stem cell transplantation.

Purpose of the Study:

  • To describe and compare the application of mixed chimerism for inducing transplantation tolerance.
  • To evaluate the efficacy of mixed chimerism in preclinical models (mice, pigs, monkeys) and human clinical settings.
  • To correlate the mechanisms underlying tolerance induction with the resulting tolerance characteristics in different species.

Main Methods:

  • Utilizing allogeneic hematopoietic stem cell transplantation to induce mixed chimerism.
  • Employing bone marrow or mobilized peripheral blood stem cell transplantation protocols.
  • Comparative analysis across species including mice, pigs, non-human primates, and human clinical data.

Main Results:

  • Mixed chimerism successfully establishes transplantation tolerance in diverse preclinical models.
  • The induction of mixed chimerism has been translated to clinical settings for achieving tolerance.
  • Mechanisms of tolerance vary but are linked to the resulting chimeric state and donor-recipient species.

Conclusions:

  • Mixed chimerism is a robust strategy for achieving transplantation tolerance across species.
  • The translation of mixed chimerism from bench to bedside highlights its clinical significance.
  • Understanding the mechanistic basis of tolerance is crucial for optimizing mixed chimerism protocols.