title: Embryonic pig pancreatic tissue for the treatment of diabetes: potential role of immune suppression with "off-the-shelf" third-party regulatory T cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Dalit
authors.initials: D
authors.lastname: Tchorsh-Yutsis
authors.forename: Yael
authors.initials: Y
authors.lastname: Zlotnikov Klionsky
authors.forename: Esther
authors.initials: E
authors.lastname: Bachar-Lustig
authors.forename: Anna
authors.initials: A
authors.lastname: Aronovich
authors.forename: Ilan
authors.initials: I
authors.lastname: Feine
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.forename: Chava
authors.initials: C
authors.lastname: Rosen
authors.forename: Rivka
authors.initials: R
authors.lastname: Bitcover
authors.forename: Smadar
authors.initials: S
authors.lastname: Eventov-Friedman
authors.forename: Helena
authors.initials: H
authors.lastname: Katchman
authors.forename: Lior
authors.initials: L
authors.lastname: Zangi
authors.forename: Orna
authors.initials: O
authors.lastname: Tal
authors.forename: Sivan
authors.initials: S
authors.lastname: Cohen
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003920:Diabetes Mellitus / Q000601:surgery*; D004622:Embryo, Mammalian / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016035:Pancreas Transplantation / Q000276:immunology*; D011409:Propylene Glycols / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013552:Swine / Q000196:embryology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D007166:Immunosuppressive Agents; D007328:Insulin; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D020123:Sirolimus