title: Hypoxia inhibits the spontaneous calcification of bone marrow-derived mesenchymal stem cells.
abstract: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the popular seed cells for regenerative medicine, and there has been a rapid increase in the number of BM-MSC-based clinical trials. However, the safety of these cells should also be closely studied. In this study, spontaneous calcification of BM-MSCs from rats was evaluated in normoxia (20% O(2)) without osteogenic medium after continuous culture for 21 days; obvious mineralized nodules were observed, which were positive for Alizarin Red, collagen-I (Col-I), osteocalcin (OC) and alkaline phosphatase (ALP), and mainly consisted of C, O and Ca elements. Interestingly, hypoxia (2% O(2)) significantly inhibited this spontaneous calcification. In addition, the ALP and calcium content of rBM-MSCs were sharply reduced. Based on RT-PCR results, the expression of osteogenic genes (Cbfa1/Runx2, Col-I, ALP, and OC) was reduced compared to that in normoxia. These results demonstrate a natural and unique characterization of rat BM-MSCs in normoxia after continuous culture and highlight the inhibiting effects of hypoxia. Finally, this study contributes to the information regarding the application of BM-MSCs in the regeneration of various tissues.
authors.affiliation: Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yong-Can
authors.initials: YC
authors.lastname: Huang
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Zhu
authors.forename: Jia-Qin
authors.initials: JQ
authors.lastname: Cai
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Huang
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Chen
authors.forename: Xiu-Qun
authors.initials: XQ
authors.lastname: Li
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Deng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002113:Calcification, Physiologic; D015687:Cell Hypoxia; D003470:Culture Media; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013052:Spectrometry, X-Ray Emission
chemical_list: D003470:Culture Media