title: Composite "thymoheart" transplantation improves cardiac allograft survival.
abstract: We have generated a novel composite organ, the thymoheart, which facilitates the contemporaneous transfer of fully vascularized and functional donor thymic tissue to the host at the time of cardiac transplantation. Composite thymoheart allografts were prepared in MHC-inbred miniature swine by implanting autologous thymic tissue into donor hearts 60-90 days before organ procurement. Thymoheart allografts and unmanipulated control hearts were then transplanted into three groups, each treated with the same 12 days of cyclosporine. MHC-matched thymohearts transplanted into euthymic recipients had a minimum survival ranging between 72 and 194 days vs. 42-64 days for unmanipulated control hearts (p = 0.02). MHC class I-disparate thymohearts transplanted into euthymic recipients had a minimum survival ranging between 64 and 191 days vs. 30-55 days for unmanipulated control hearts (p = 0.01). MHC class I-disparate thymohearts transplanted into thymectomized recipients survived between 41 and 70 days vs. 8-27 days for unmanipulated control hearts (p = 0.01). Cellular and humoral functional assays, and skin grafting, confirmed the presence of donor-specific hyporesponsiveness in long-term thymoheart allografts recipients. The transfer of vascularized, functional donor thymic tissue to the host at the time of cardiac transplantation may provide a novel approach to the induction of tolerance in human heart transplant recipients.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Menard
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Schwarze
authors.forename: James S
authors.initials: JS
authors.lastname: Allan
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Johnston
authors.forename: Kwabena
authors.initials: K
authors.lastname: Mawulawde
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Houser
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Allison
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: Joren C
authors.initials: JC
authors.lastname: Madsen
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D005434:Flow Cytometry; D006239:Haplotypes; D006321:Heart / Q000502:physiology; D016027:Heart Transplantation / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007150:Immunohistochemistry / Q000379:methods; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016377:Organ Transplantation; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D016572:Cyclosporine