Rat-to-Chinese tree shrew heart transplantation is a novel small animal model to study non-Gal-mediated discordant xenograft humoral rejection.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Chen, W; Wu, Y; Shimizu, A; Lian, Y; Tasaki, M; Villani, V; Moran, S; Xia, J; Yamada, K; Qi, Z

Published Date

  • November 20, 2015

Published In

Volume / Issue

  • 22 / 6

Start / End Page

  • 468 - 475

PubMed ID

  • 26589781

Pubmed Central ID

  • PMC5257258

Electronic International Standard Serial Number (EISSN)

  • 1399-3089

International Standard Serial Number (ISSN)

  • 0908-665X

Digital Object Identifier (DOI)

  • 10.1111/xen.12211

Language

  • eng