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Rat‐to‐Chinese tree shrew heart transplantation is a novel small animal model to study non‐Gal‐mediated discordant xenograft humoral rejection
Author(s) -
Chen WeiLi,
Wu Yuan,
Shimizu Akira,
Lian YinLong,
Tasaki Masayuki,
Villani Vincenzo,
Moran Shan,
Xia JunJie,
Yamada Kazuhiko,
Qi ZhongQuan
Publication year - 2015
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12211
Subject(s) - xenotransplantation , immunosuppression , transplantation , antibody , andrology , immunology , biology , flow cytometry , medicine
Since α‐1,3‐galactosyltransferase knockout (GalT‐ KO ) pigs became available, there has been an increasing interest in non‐Gal natural antibody ( nA b)‐mediated xenograft rejection. To better understand mechanisms of non‐Gal nA b‐mediated rejection, a simple small animal model without gene manipulation would be extremely valuable. Here, we tested whether the Chinese tree shrew ( CTS ), which is a small‐sized mammal that is phylogenetically close to primates, could serve as a model for discordant xenograft rejection. Methods Study 1: Expression of α‐Gal antigens in hearts and kidneys of CTS s and rats was assessed by IB 4 lectin binding. Presence of anti‐Gal and anti‐non‐Gal IgM and IgG nA b in CTS sera was tested by FACS using Gal+ and Gal TKO PBMC as well as BSA ‐ ELISA . Study 2: Rat hearts were transplanted into CTS recipients (group 1, n = 7), and CTS hearts were transplanted in rats [n = 10; seven received no immunosuppression (group 2) and three received FK 506 + leflunomide (group 3)]. Results Study 1: Both CTS s and rats had α‐Gal expression in hearts and kidneys. ELISA showed CTS s do not have anti‐Gal nA b, and flow cytometry indicated CTS s have anti‐non‐Gal IgM and IgG nA b in serum. Study 2: Rat hearts in CTS s were uniformly rejected within 35 mins, while CTS hearts in rats continued beating until day 5 without immunosuppression, and up to day 8 with immunosuppression. Conclusion Rat‐to‐ CTS heart transplantation is a discordant xenotransplant model, CTS ‐to‐Rat heart transplantation is a concordant xenotransplant model. CTS s are valuable small animals to study mechanisms and strategies to avoid non‐Gal nA b‐mediated xenograft rejection.