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Mol Med. 2015 Mar 23;21:185-96. doi: 10.2119/molmed.2014.00188.

Human Parthenogenetic Embryonic Stem Cell-Derived Neural Stem Cells Express HLA-G and Show Unique Resistance to NK Cell-Mediated Killing.

Author information

1
Institute for Medical Radiology and Cell Research (MSZ) in the Center for Experimental Molecular Medicine (ZEMM), University of Würzburg, Würzburg, Germany.
2
Center for Molecular and Human Genetics, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
3
University Children's Hospital Würzburg, Pediatric Hematology/Oncology, Würzburg, Germany.
4
Department of Neurosurgery, Section for Experimental Tumor Immunology, University of Würzburg, Würzburg, Germany.
5
University of Würzburg Medical School, Department of Obstetrics and Gynecology, Section for Experimental Tumor Immunology, University of Würzburg, Würzburg, Germany.

Abstract

Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro mixed lymphocyte reaction assay resulted in less proliferation of peripheral blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression analyses of immune regulatory factors revealed higher HLA-G levels in PG compared with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG NSCs. Together this indicates that PG NSCs have unique immunological properties due to elevated HLA-G expression.

PMID:
25811991
PMCID:
PMC4503648
DOI:
10.2119/molmed.2014.00188
[Indexed for MEDLINE]
Free PMC Article

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