Role of Wnt signaling in proliferation of human bone marrow-derived mesenchymal stem cells
Human mesenchymal stem cell (hMSC) is an attractive source of adult stem cells for the therapeutic use in regenerative medicine. These cells are usually culture expanded prior to their application. However, their proliferation and differentiation potential were gradually decreased during in vitro expansion. Wingless-related MMTV integration site (Wnt) is well known signaling molecules that implicated in mesenchymal differentiation during development, but the role in proliferation of hMSCs is not well known. In this study, we investigated the effect of Wnt signaling molecules on the proliferation of hMSCs. The relative expression of secreted frizzled-related protein 1, an inhibitor for canonical Wnt signaling, was declined with passage, but nuclear β-catenin level was not related to sFRP1. Interestingly, specific knockdown of sFRP1 by shRNA in hMSCs decreased their proliferation rate, whereas recombinant sFRP1 protein accelerates the growth of cells. These findings suggest that sFRP1 has a pivotal role in proliferation of hMSCs during in vitro culture expansion. Additionally, we found that the expression levels of Wnt5a and retinoic-acid orphan related receptor α were gradually increased with passage. These observations suggest that non-canonical Wnt pathway is a potent regulator of hMSC proliferation.
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