title: Serum free cultured bone marrow mesenchymal stem cells as a platform to characterize the effects of specific molecules.
abstract: Human mesenchymal stem cells (hMSC) are easily isolated from the bone marrow by adherence to plastic surfaces. These cells show self-renewal capacity and multipotency. A unique feature of hMSC is their capacity to survive without serum. Under this condition hMSC neither proliferate nor differentiate but maintain their biological properties unaffected. Therefore, this should be a perfect platform to study the biological effects of defined molecules on these human stem cells. We show that hMSC treated for five days with retinoic acid (RA) in the absence of serum undergo several transcriptional changes causing an inhibition of ERK related pathways. We found that RA induces the loss of hMSC properties such as differentiation potential to either osteoblasts or adipocytes. We also found that RA inhibits cell cycle progression in the presence of proliferating signals such as epidermal growth factor (EGF) combined with basic fibroblast growth factor (bFGF). In the same manner, RA showed to cause a reduction in cell adhesion and cell migration. In contrast to these results, the addition of EGF+bFGF to serum free cultures was enough to upregulate ERK activity and induce hMSC proliferation and cell migration. Furthermore, the addition of these factors to differentiation specific media instead of serum was enough to induce either osteogenesis or adipogenesis. Altogether, our results show that hMSC's ability to survive without serum enables the identification of signaling factors and pathways that are involved in their stem cell biological characteristics without possible serum interferences.
authors.affiliation: Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Solmesky
authors.forename: Sharon
authors.initials: S
authors.lastname: Lefler
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob-Hirsch
authors.forename: Shlomo
authors.initials: S
authors.lastname: Bulvik
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Miguel
authors.initials: M
authors.lastname: Weil
mesh_terms: D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008875:Middle Aged; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism; D055815:Young Adult
chemical_list: D016895:Culture Media, Serum-Free; D016222:Fibroblast Growth Factor 2; D014212:Tretinoin; D004815:Epidermal Growth Factor