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Regulation of stemness capability of human bone marrow-derived mesenchymal stem cells

Lee, Jieun; Park, Jinsung; Lee, Young-Don; Suh-Kim, Haeyoung; Kim, Sung-Soo
Department of Anatomy
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, during in vitro long-term culture for expansion, hMSC lose their multipotentency and proliferation capability. The extent of multi-lineage differentiation ability of stem cells is believed to be associated with the potential for expression of developmentally- and differentiation- regulated genes. For this purpose, firstly we examined and compared proliferation rates and differentiation potential of hMSCs expanded under different culture conditions. We also specifically evaluated gene expression profile of Wingless-related MMTV integration site (Wnt) pathway related genes. Long-term culture expanded hMSCs demonstrated morphological enlargement, proliferation arrest, and limited differentiation potential. Several developmentally-regulated genes were found to be up- or down- regulated depending on the passage of hMSCs. Interestingly, by overexpression or knockdown experiments, we found that some of genes were shown to be required for the proliferation of hMSCs. These findings suggest that developmentally-regulated gene has a pivotal role in self-renewal of hMSCs during in vitro culture expansion.
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