WeiLi Chen1, Yuan Wu1, Akira Shimizu2, YinLong Lian1, Masayuki Tasaki2, Vincenzo Villani2, Shannon Moran2, JunJie Xia1, Kazuhiko Yamada2,3,4, ZhongQuan Qi1. 1. Organ Transplantation Institute, Xiamen University, Xiamen, Fujian Province, China. 2. Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 3. Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA. 4. Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
Abstract
UNLABELLED: Since α-1,3-galactosyltransferase knockout (GalT-KO) pigs became available, there has been an increasing interest in non-Gal natural antibody (nAb)-mediated xenograft rejection. To better understand mechanisms of non-Gal nAb-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 CTSs and rats was assessed by IB4 lectin binding. Presence of anti-Gal and anti-non-Gal IgM and IgG nAb in CTS sera was tested by FACS using Gal+ and GalTKO 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 FK506 + leflunomide (group 3)]. RESULTS: Study 1: Both CTSs and rats had α-Gal expression in hearts and kidneys. ELISA showed CTSs do not have anti-Gal nAb, and flow cytometry indicated CTSs have anti-non-Gal IgM and IgG nAb in serum. Study 2: Rat hearts in CTSs 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. CTSs are valuable small animals to study mechanisms and strategies to avoid non-Gal nAb-mediated xenograft rejection.
UNLABELLED: Since α-1,3-galactosyltransferase knockout (GalT-KO) pigs became available, there has been an increasing interest in non-Gal natural antibody (nAb)-mediated xenograft rejection. To better understand mechanisms of non-GalnAb-mediated rejection, a simple small animal model without gene manipulation would be extremely valuable. Here, we tested whether theChinese 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 CTSs and rats was assessed by IB4 lectin binding. Presence of anti-Gal and anti-non-Gal IgM and IgG nAb in CTS sera was tested by FACS using Gal+ and GalTKO PBMC as well as BSA-ELISA. Study 2: Rathearts were transplanted into CTS recipients (group 1, n = 7), and CTShearts were transplanted in rats [n = 10; seven received no immunosuppression (group 2) and three received FK506 + leflunomide (group 3)]. RESULTS: Study 1: Both CTSs and rats had α-Gal expression in hearts and kidneys. ELISA showed CTSs do not have anti-GalnAb, and flow cytometry indicated CTSs have anti-non-Gal IgM and IgG nAb in serum. Study 2: Rathearts in CTSs were uniformly rejected within 35 mins, while CTShearts in rats continued beating until day 5 without immunosuppression, and up to day 8 with immunosuppression. CONCLUSION:Rat-to-CTSheart transplantation is a discordant xenotransplant model, CTS-to-Ratheart transplantation is a concordant xenotransplant model. CTSs are valuable small animals to study mechanisms and strategies to avoid non-GalnAb-mediated xenograft rejection.
Authors: Susan L Orloff; Daniel N Streblow; Cecilia Soderberg-Naucler; Qiang Yin; Craig Kreklywich; Christopher L Corless; Patricia A Smith; Christopher B Loomis; Lisa K Mills; Judith W Cook; Catherine A Bruggeman; Jay A Nelson; Cynthia R Wagner Journal: Transplantation Date: 2002-03-15 Impact factor: 4.939
Authors: Liangxue Lai; Donna Kolber-Simonds; Kwang-Wook Park; Hee-Tae Cheong; Julia L Greenstein; Gi-Sun Im; Melissa Samuel; Aaron Bonk; August Rieke; Billy N Day; Clifton N Murphy; David B Carter; Robert J Hawley; Randall S Prather Journal: Science Date: 2002-01-03 Impact factor: 47.728
Authors: Carol J Phelps; Chihiro Koike; Todd D Vaught; Jeremy Boone; Kevin D Wells; Shu-Hung Chen; Suyapa Ball; Susan M Specht; Irina A Polejaeva; Jeff A Monahan; Pete M Jobst; Sugandha B Sharma; Ashley E Lamborn; Amy S Garst; Marilyn Moore; Anthony J Demetris; William A Rudert; Rita Bottino; Suzanne Bertera; Massimo Trucco; Thomas E Starzl; Yifan Dai; David L Ayares Journal: Science Date: 2002-12-19 Impact factor: 47.728