TY  - JOUR
A1  - Herrmann, Marietta
A1  - Hildebrand, Maria
A1  - Menzel, Ursula
A1  - Fahy, Niamh
A1  - Alini, Mauro
A1  - Lang, Siegmund
A1  - Benneker, Lorin
A1  - Verrier, Sophie
A1  - Stoddart, Martin J.
A1  - Bara, Jennifer J.
T1  - Phenotypic characterization of bone marrow mononuclear cells and derived stromal cell populations from human iliac crest, vertebral body and femoral head
JF  - International Journal of Molecular Sciences
N2  - (1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14–91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45−CD34−CD73+, CD45−CD34−CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.
KW  - bone marrow stromal cells
KW  - MSC
KW  - pericytes
KW  - femoral head
KW  - vertebral body
KW  - iliac crest
KW  - chondrogenesis
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285054
SN  - 1422-0067
VL  - 20
IS  - 14
ER  - 
TY  - JOUR
A1  - Müller-Deubert, Sigrid
A1  - Seefried, Lothar
A1  - Krug, Melanie
A1  - Jakob, Franz
A1  - Ebert, Regina
T1  - Epidermal growth factor as a mechanosensitizer in human bone marrow stromal cells
JF  - Stem Cell Research
N2  - Epidermal growth factors (EGFs) e.g. EGF, heparin-binding EGF and transforming growth factor alpha and their receptors e.g. EGFR and ErbB2 control proinflammatory signaling and modulate proliferation in bone marrow stromal cells (BMSC). Interleukin-6 and interleukin-8 are EGF targets and participate in the inflammatory phase of bone regeneration via non-canonical wnt signaling. BMSC differentiation is also influenced by mechanical strain-related activation of ERK1/2 and AP-1, but the role of EGFR signaling in mechanotransduction is unclear. We investigated the effects of EGFR signaling in telomerase-immortalized BMSC, transfected with a luciferase reporter, comprising a mechanoresponsive AP1 element, using ligands, neutralizing antibodies and EGFR inhibitors on mechanotransduction and we found that EGF via EGFR increased the response to mechanical strain. Results were confirmed by qPCR analysis of mechanoresponsive genes. EGF-responsive interleukin-6 and interleukin-8 were synergistically enhanced by EGF stimulation and mechanical strain. We show here in immortalized and primary BMSC that EGFR signaling enhances mechanotransduction, indicating that the EGF system is a mechanosensitizer in BMSC. Alterations in mechanosensitivity and -adaptation are contributors to age-related diseases like osteoporosis and the identification of a suitable mechanosensitizer could be beneficial. The role of the synergism of these signaling cascades in physiology and disease remains to be unraveled.
KW  - mechanotransduction
KW  - bone marrow stromal cells
KW  - epidermal growth factor
KW  - signaling
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170247
VL  - 24
ER  -