Journal
CELL TRANSPLANTATION
Volume 26, Issue 2, Pages 365-377Publisher
SAGE PUBLICATIONS INC
DOI: 10.3727/096368916X693040
Keywords
Human mesenchymal stem cells (hMSCs); Self-renewing cells; Epidermal growth factor (EGF); beta-Catenin
Funding
- National Research Foundation of Korea (NRF) - Basic Science Research Program through the Ministry of Education, Science and Technology [NRF-2011-0011716]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI13C0954]
- Ewha Womans University School of Medicine
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Human mesenchymal stem cells (hMSCs) are self-renewing cells with the ability to differentiate into organized, functional network of cells. Recent studies have revealed that activation of the Wnt/beta-catenin pathway by a glycogen synthase kinase (GSK)-3-specific pharmacological inhibitor, Bio, results in the maintenance of self-renewal in both mouse and human ES cells. The molecular mechanism behind the maintenance of hMSCs by these factors, however, is not fully understood. We found that rEGF enhances the level of beta-catenin, a component of the Wnt/beta-catenin signaling pathway. Furthermore, it was found that beta-catenin upregulates Nanog. EGF activates the beta-catenin pathway via the Ras protein and also increased the Nanog protein and gene expression levels 2 h after rEGF treatment. These results suggest that adding EGF can enhance beta-catenin and Nanog expression in MSCs and facilitate EGF-mediated maintenance of MSC self-renewal. EGF was shown to augment MSC proliferation while preserving early progenitors within MSC population and thus did not induce differentiation. Thus, EGF not only can be used to expand MSC in vitro but also be utilized to autologous transplantation of MSCs in vivo.
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