TY  - JOUR
A1  - Steinert, Andre F.
A1  - Kunz, Manuela
A1  - Prager, Patrick
A1  - Göbel, Sascha
A1  - Klein-Hitpass, Ludger
A1  - Ebert, Regina
A1  - Nöth, Ulrich
A1  - Jakob, Franz
A1  - Gohlke, Frank
T1  - Characterization of bursa subacromialis-derived mesenchymal stem cells
JF  - Stem Cell Research & Therapy
N2  - Introduction
The bursa subacromialis (BS) provides the gliding mechanism of the shoulder and regenerates itself after surgical removal. Therefore, we explored the presence of mesenchymal stem cells (MSCs) within the human adult BS tissue and characterized the BS cells compared to MSCs from bone marrow (BMSCs) on a molecular level.

Methods
BS cells were isolated by collagenase digest from BS tissues derived from patients with degenerative rotator cuff tears, and BMSCs were recovered by adherent culture from bone-marrow of patients with osteoarthritis of the hip. BS cells and BMSCs were compared upon their potential to proliferate and differentiate along chondrogenic, osteogenic and adipogenic lineages under specific culture conditions. Expression profiles of markers associated with mesenchymal phenotypes were comparatively evaluated by flow cytometry, immunohistochemistry, and whole genome array analyses.

Results
BS cells and BMSCs appeared mainly fibroblastic and revealed almost similar surface antigen expression profiles, which was \(CD44^+, CD73^+, CD90^+, CD105^+, CD106^+\),\(STRO-1^+, CD14^−, CD31^−, CD34^− , 
CD45^−, CD144^−\). Array analyses revealed 1969 genes upregulated and 1184 genes downregulated in BS cells vs. BMSCs, indicating a high level of transcriptome similarity. After 3 weeks of differentiation culture, BS cells and BMSCs showed a similar strong chondrogenic, adipogenic and osteogenic potential, as shown by histological, immunohistochemical and RT-PCR analyses in contrast to the respective negative controls.

Conclusions
Our in vitro characterizations show that BS cells fulfill all characteristics of mesenchymal stem cells, and therefore merit further attention for the development of improved therapies for various shoulder pathologies.
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126446
VL  - 6
IS  - 114
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  -