ORIGINAL ARTICLE

Cell Research (2009): 507-518
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Low immunogenicity of endothelial derivatives from rat embryonic stem cell-like cells

Juliane Ladhoff¹, Michael Bader², Sabine Brösel¹, Elke Effenberger¹, Dirk Westermann³, Hans-Dieter Volk^1,4 and Martina Seifert^1,4

Correspondence: Martina Seifert, Tel: +49-30-450524198; Fax: +49-30-450524907 E-mail: martina.seifert@charite.de

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Embryonic stem cells (ESC) are suggested to be immune-privileged, but they carry the risk of uncontrolled expansion and malignancy. Upon differentiation they lose their tumor-forming capacity, but they become immunogenic by the expression of a normal set of MHC molecules. This immunogenicity might trigger rejection after application in regenerative therapies. In this study MHC expression of and immune responses to endothelial derivatives of rat embryonic stem cell-like cells (RESC) under inflammatory conditions were determined in comparison to primary rat aortic endothelial cells (ECs). Cellular as well as humoral allo-recognition was analyzed in vitro. In addition, immune reactions in vivo were assessed by allo-antibody production and determination of interferon-γ (IFNγ)-secreting allo-reactive T cells. RESC derivatives expressed low but significant levels of MHC class I, and no MHC class II. In response to IFNγ MHC class I expression was enhanced, while class II transactivator induction failed completely in these cells; MHC class II expression remained consistently absent. Functionally, the RESC derivatives showed a reduced allo-stimulatory capacity, protection against humoral allo-recognition in vitro and a slightly diminished susceptibility to cytotoxic T cell lysis. Furthermore, in vivo experiments demonstrated that these cells do not trigger host immune reactions, characterized by no allo-antibody production and no induction of allo-reactive memory T cells. Our results show that endothelial derivatives of RESC have a distinctive reduced immunogenic potency even under inflammatory conditions.

Cell Research (2009) 19:507–518. doi: 10.1038/cr.2009.21; published online 24 February 2009

Keywords: stem cells, cell differentiation, endothelial cells, MHC, CIITA, immunogenicity