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Ann Thorac Surg 2000;70:131-138
© 2000 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Mixed hematopoietic chimerism induces long-term tolerance to cardiac allografts in miniature swine

^a Division of Cardiac Surgery and Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Address reprint requests to Dr Madsen, Division of Cardiac Surgery, Massachusetts General Hospital, EDR 105, 55 Fruit St, Boston, MA 02114
e-mail: madsen{at}helix.mgh.harvard.edu

Presented at the Thirty-sixth Annual Meeting of the Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 31–Feb 2, 2000.

Background. Tolerance to cardiac allografts has not been achieved in large animals using methods that are readily applicable to human recipients. We investigated the effects of mixed hematopoietic chimerism on cardiac allograft survival and chronic rejection in miniature swine

Methods. Recipients were T-cell depleted using a porcine CD3 immunotoxin, and each received either of two nonmyeloablative preparative regimens previously demonstrated to permit the establishment of stable mixed hematopoietic chimerism across MHC-matched, minor-antigen–mismatched histocompatibility barriers. Five to 12 months after the chimerism was induced, hearts from the original cell donors were heterotopically transplanted into the stable mixed chimeras.

Results. Cardiac allografts transplanted into untreated recipients across similar minor antigen barriers were rejected within 44 days (within 21, 28, 35, 39, 44 days among individual study subjects). In contrast, hearts transplanted into the mixed chimeras were all accepted long term ( > 153, > 225, > 286, > 362 days) without immunosuppressive drugs and developed minimal vasculopathy.

Conclusions. Mixed hematopoietic chimerism, established in miniature swine using clinically relevant, nonmyeloablative conditioning regimens, permits long-term cardiac allograft survival without chronic immunosuppressive therapy, significant vasculopathy, or graft-versus-host disease.

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Discussion
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