TY  - JOUR
A1  - Schmitt, Jessica
A1  - Eckardt, Sigrid
A1  - Schlegel, Paul G
A1  - Sirén, Anna-Leena
A1  - Bruttel, Valentin S
A1  - McLaughlin, K John
A1  - Wischhusen, Jörg
A1  - Müller, Albrecht M
T1  - Human parthenogenetic embryonic stem cell-derived neural stem cells express HLA-G and show unique resistance to NK cell-mediated killing
JF  - Molecular Medicine
N2  - 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.
KW  - brain development
KW  - immune response
KW  - T lymphocytes
KW  - blastocysts
KW  - lines
KW  - HLA-G gene
KW  - mhc molecules
KW  - nervous system
KW  - in vitro
KW  - stem/progenitor cells
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149170
VL  - 21
IS  - 2101185
ER  - 
TY  - JOUR
A1  - Ebert, Regina
A1  - Benisch, Peggy
A1  - Krug, Melanie
A1  - Zeck, Sabine
A1  - Meißner-Weigl, Jutta
A1  - Steinert, Andre
A1  - Rauner, Martina
A1  - Hofbauer, Lorenz
A1  - Jakob, Franz
T1  - Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells
JF  - Stem Cell Research
N2  - The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation andmineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1\(\beta\), CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis.
KW  - human atherosclerotic lesions
KW  - senescence
KW  - expression
KW  - toll-like receptor
KW  - mineralization
KW  - osteogenic differentiation
KW  - serum amyloid A
KW  - inflammation
KW  - mesenchymal stem cells
KW  - WNT5A
KW  - model
KW  - lines
KW  - stromal cells
KW  - RT-PCR
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148491
VL  - 15
ER  -