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Embryonic Stem Cells |
1 Roy J. and Lucille A. Carver College of Medicine, University of Iowa & VA Medical Center Iowa City, Iowa City, Iowa
2 Roy J. and Lucille A. Carver College of Medicine, University of Iowa & VA Medical Center Iowa City, Iowa City, Iowa; Immunology Graduate Program, University of Iowa, Iowa City, Iowa
* To whom correspondence should be addressed. E-mail: Nicholas-zavazava{at}uiowa.edu.
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Abstract |
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Embryonic stem cells (ESC) 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 ESC fail to stimulate T cells, but abrogate ongoing alloresponses by a process that requires cell-cell contact. We further show that despite a high expression of the NKG2D ligand RAE-1 (retinoic acid early inducible-1) by mouse ESC, they remain resistant to natural killer cell lysis. In vivo, allogeneic mouse ESC 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 MHC. Immune-histochemical 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 non-differentiated mouse embryonic stem cells are non-immunogenic and appear to populate lymphoid tissues in vivo leading to T cell deletion by apoptosis.
Key Words. embryonic stem cells, engraftment, apoptosis, mixed chimerism, RAE-1
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  D. C. Wu, A. S. Boyd, and K. J. Wood Embryonic Stem Cells and Their Differentiated Derivatives Have a Fragile Immune Privilege but Still Represent Novel Targets of Immune Attack Stem Cells, August 1, 2008; 26(8): 1939 - 1950. [Abstract] [Full Text] [PDF]
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 K.-M. Chan, S. Bonde, H. Klump, and N. Zavazava Hematopoiesis and immunity of HOXB4-transduced embryonic stem cell-derived hematopoietic progenitor cells Blood, March 15, 2008; 111(6): 2953 - 2961. [Abstract] [Full Text] [PDF]
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