Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Hepatocyte Growth Factor-mediated Regulation of OCT4 in human Mesenchymal Stem Cells

  • Ji-Eun Oh (Department of Biomedical Laboratory Science, Far East University) ;
  • Jung-Yoon Yoo (Department of Biomedical Laboratory Science, Yonsei University Mirae Campus) ;
  • Eun Ju Lee (Biomedical Research Institute, Seoul National University Hospital) ;
  • Sung Ryul Yu (Department of Clinical Laboratory Science, Semyung University)
  • Received : 2024.09.04
  • Accepted : 2024.09.24
  • Published : 2024.09.30
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Abstract

Mesenchymal stem cells (MSCs) hold great promise as a source of stem cells for therapy, but several limitations remain. We previously proposed that human embryonic stem cell-derived MSCs (hE-MSCs) expressing higher hepatocyte growth factor (HGF) levels were better alternatives, exhibiting greater expandability in vitro and greater therapeutic capacity in vivo. In this study, we aimed to examine the regulation of OCT4 expression in stem cells and to elucidate its underlying mechanism of transcriptional regulation of OCT4. We detected higher expression of OCT4, a stemness-associated gene in hE-MSCs than in human bone marrow-derived MSCs (hBM-MSCs). To determine the underlying regulatory mechanism of OCT4 expression in human MSCs (hMSCs), ELISA was performed using cell culture supernatants of hMSCs. Unlike fibroblast growth factor 2 or vascular endothelial growth factor, HGF was strongly expressed in hE-MSCs, also HGF treatment significantly increased OCT4 expression in hBM-MSC. Moreover, senescence-associated heterochromatin foci were decreased in HGF-treated hBM-MSCs compared with those in the HGF non-treated group. HGF increased Rb phosphorylation, and we confirmed the increased binding of E2F1 to the OCT4 promoter region at -233 from the transcription start point in the presence of HGF. Taken together, these results suggest that HGF-mediated regulation of OCT4 via E2F1 can help enhance the lifespan of hBM-MSCs during in vitro expansion.

Keywords

References

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