Embryonic stem cells, derived either after in vitro fertilization or nuclear transfer, prolong survival of semiallogeneic heart transplants.

نویسندگان

  • Barbara Imberti
  • Federica Casiraghi
  • Daniela Cugini
  • Nadia Azzollini
  • Paola Cassis
  • Marta Todeschini
  • Samantha Solini
  • Vittorio Sebastiano
  • Maurizio Zuccotti
  • Silvia Garagna
  • Carlo Alberto Redi
  • Marina Noris
  • Marina Morigi
  • Giuseppe Remuzzi
چکیده

Tolerance induction toward allogeneic organ grafts represents one of the major aims of transplantation medicine. Stem cells are promising candidates for promoting donor-specific tolerance. In this study, we investigated the immunomodulatory properties of murine embryonic stem cells (ESCs), obtained either by in vitro fertilization (IVF-ESCs) or by nuclear transfer (NT-ESCs), in heart transplant mouse models. IVF-ESCs did not prolong the survival of fully allogeneic cardiac transplants but significantly prolonged the survival of semiallogeneic hearts from the same ESC donor strain for >100 d in 44% of the animals. However, 28% of transplanted animals infused with IVF-ESCs experienced development of a teratoma. NT-ESCs similarly prolonged semiallogeneic heart graft survival (>100 d in 40% of the animals) but were less teratogenic. By in vitro studies, IVF-ESC and NT-ESC immunoregulation was mediated both by cell contact-dependent mechanisms and by the release of soluble factors. By adding specific inhibitors, we identified PGE(2) as a soluble mediator of ESC immunoregulation. Expansion of regulatory T cells was found in lymphoid organs and in the grafts of IVF-ESC- and NT-ESC-tolerized mice. Our study demonstrates that both IVF-ESCs and NT-ESCs modulate recipient immune response toward tolerance to solid organ transplantation, and that NT-ESCs exhibit a lower tendency for teratoma formation. Because NT-ESCs are obtained by NT of a somatic cell from living individuals into an enucleated oocyte, they could represent a source of donor-derived stem cells to induce tolerance to solid organ allograft.

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Transplants Prolong Survival of Semiallogeneic Heart In Vitro Fertilization or Nuclear Transfer, Embryonic Stem Cells, Derived Either after

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عنوان ژورنال:
  • Journal of immunology

دوره 186 7  شماره 

صفحات  -

تاریخ انتشار 2011