Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

Li Lu, Hui-Fang Song, Wei-Guo Zhang, Xue-Qin Liu, Qian Zhu, Xiao-Long Cheng, Gui-Jiao Yang, Ang Li, Zhi-Cheng Xiao

    Research output: Contribution to journalArticleResearchpeer-review

    13 Citations (Scopus)

    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 18alpha-glycyrrhetinic acid (18alpha-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.
    Original languageEnglish
    Pages (from-to)121 - 127
    Number of pages7
    JournalBiochemical and Biophysical Research Communications
    Volume422
    Issue number1
    DOIs
    Publication statusPublished - 2012

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