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Presenter: Radbeh, Torabi, Boston, MA, USA
Authors: Radbeh Torabi, Joseph Scalea, Angelo Leto Barone, David Leonard, Brad Gillon, Taylor Cormack, Mark Randolph, David Sachs, Kazuhiko Yamada, Curtis Cetrulo Jr.
Radbeh Torabi1,2, Joseph Scalea2, Angelo Leto Barone1,2, David Leonard1,2, Brad Gillon2, Taylor Cormack2, Mark Randolph1,2, David Sachs2, Kazuhiko Yamada2, Curtis Cetrulo Jr.1,2.
1Department of Plastic Surgery, 2Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Introduction: We have previously reported that a 12-day course of high dose FK506 uniformly facilitates the induction of tolerance to fully MHC mismatched kidneys in MGH miniature swine. However, this induction strategy has proven unsuccessful for cardiac allografts, likely due to peripheral tolerance-induction properties unique to the kidney. We investigated whether this protocol would allow tolerance of a gracilis myocutaneous free flap composite tissue allografts (CTA) across a full MHC mismatch.
Methods: MGH miniature swine received CTAs consisting of either a gracilis muscle flap and recipient autologous split-thickness skin graft (group I) or gracilis myocutaneous flap (group II). Infusion pumps were utilized to maintain FK506 levels at 35-80 ng/ml by continuous intravenous infusion which permits tolerance induction of full allogeneic kidneys. CTAs were examined daily and biopsies of skin and muscle were taken at days 14, 21 and at times of suspected rejection.
Results: Incipient clinical rejection with histologic evidence of mild interstitial cell infiltrate, was noted by PTD14, after cessation of FK506. CTAs in both groups demonstrated full clinical rejection of all tissue components by PTD 21. Histological examination of excised CTA grafts showed diffuse interstitial cell infiltrate and hemorrhages, indicating cellular and humoral rejection.
Conclusions: These data indicate that skeletal muscle allografts and myocutaneous flaps, like cardiac allografts, but unlike renal allografts, are not able to induce tolerance following high-dose calcineurin inhibition for 12 days across a full MHC mismatch. Further studies are underway in this model with increased duration of FK506, similar regimens in class I-disparate transplants, and regulatory-cell induction strategies.
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