Immunogenicity and engraftment of mouse embryonic stem cells in allogeneic recipients

Stem Cells. 2006 Oct;24(10):2192-201. doi: 10.1634/stemcells.2006-0022. Epub 2006 Jun 22.


Embryonic stem cells (ESCs) are pluripotent and therefore able to differentiate both in vitro and in vivo into specialized tissues under appropriate conditions, a property that could be exploited for cellular therapies. However, the immunological nature of these cells in vivo has not been well understood. In vitro, mouse-derived ESCs fail to stimulate T cells, but they abrogate ongoing alloresponses by a process that requires cell-cell contact. We further show that despite a high expression of the NKG2D ligand retinoic acid early inducible-1 by mouse ESCs, they remain resistant to natural killer cell lysis. In vivo, allogeneic mouse ESCs populate the thymus, spleen, and liver of sublethally irradiated allogeneic host mice, inducing apoptosis to T cells and establishing multilineage mixed chimerism that significantly inhibits alloresponses to donor major histocompatibility complex antigens. Immunohistochemical imaging revealed a significant percentage of ESC-derived cells in the splenic marginal zones, but not in the follicles. Taken together, the data presented here reveal that nondifferentiated mouse embryonic stem cells are non-immunogenic and appear to populate lymphoid tissues in vivo, leading to T-cell deletion by apoptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cell Differentiation / immunology
  • Cell Line
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / immunology
  • Liver / cytology
  • Liver / immunology
  • Mice
  • Spleen / cytology
  • Spleen / immunology
  • Stem Cell Transplantation / methods*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transplantation Chimera / immunology
  • Transplantation Chimera / metabolism
  • Transplantation, Homologous / immunology
  • Transplantation, Homologous / methods*