title: Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion.
abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18α-glycyrrhetinic acid (18α-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.
authors.affiliation: Department of Anatomy, Shanxi Medical University, Taiyuan 030001, China. luli7300@126.com
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Song
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Zhang
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Cheng
authors.forename: Gui-Jiao
authors.initials: GJ
authors.lastname: Yang
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000201:enzymology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors; D017154:Stromal Cells / Q000166:cytology* / Q000201:enzymology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde