Embryonic pig pancreatic tissue for the treatment of diabetes: Potential role of immune suppression with off-the-shelf third-party regulatory T cells

Dalit Tchorsh-Yutsis, Yael Zlotnikov Klionsky, Esther Bachar-Lustig, Anna Aronovich, Ilan Feine, Elias Shezen, Chava Rosen, Rivka Bitcover, Smadar Eventov-Friedman, Helena Katchman, Lior Zangi, Orna Tal, Sivan Cohen, Yair Reisner

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background. Xenogeneic embryonic pancreatic tissue can provide an attractive alternative for organ replacement therapy. However, immunological rejection represents a major obstacle. This study examines the potential of regulatory T cells (Tregs) in the prevention of E42 pancreas rejection. Methods. To develop new approaches to combat rejection, we evaluated engraftment, growth, and development of E42 pig pancreatic tissue in mice treated with ex vivo expanded Tregs in combination with T-cell debulking and the conventional immunosuppressive drugs, rapamycin and FTY720. Results. Transplantation of E42 pig pancreas into C57BL/6 mice immunosuppressed by this protocol resulted in complete rejection within less than 6 weeks. In contrast, additional treatment with a single infusion of ex vivo expanded third-party Tregs markedly delayed the onset of graft rejection to 10 weeks. The infusion of Tregs was associated with a significant reduction in CD4 and CD8 expansion in the lymph nodes and other peripheral organs at the priming stages after implantation. Freezing and thawing of the Tregs did not affect their efficacy, indicating the potential of Tregs banking. Conclusion. Considering the technical difficulties encountered in the generation of Tregs from patients or from specific donors, our results demonstrate the feasibility of using "off-the-shelf" fresh or frozen third-party Tregs to control rejection in organ transplantation.

Original languageEnglish
Pages (from-to)398-405
Number of pages8
JournalTransplantation
Volume91
Issue number4
DOIs
StatePublished - 27 Feb 2011
Externally publishedYes

Keywords

  • Pancreas
  • T regulatory cells
  • Transplantation
  • Xenotransplanataion

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