FZD5 regulates cellular senescence in human mesenchymal stem/stromal cells
| Autor: | Daisuke Araki, Daisuke Shimojo, Masunori Kajikawa, Seiko Harada, Chihiro Akazawa, Hideyuki Okano, Yoshimi Kawamura, Sadafumi Suzuki, Yo Mabuchi, Takashi Suyama, Yumi Matsuzaki, Jun Kohyama |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Senescence endocrine system senescence Stromal cell Cell Cell- and Tissue-Based Therapy Biology Mesenchymal Stem Cell Transplantation Cell therapy 03 medical and health sciences 0302 clinical medicine medicine Humans FZD5 receptor human mesenchymal stem/stromal cells Cells Cultured Cellular Senescence Cell Proliferation Gene knockdown aging Mesenchymal stem cell Wnt signaling pathway Cell Differentiation Mesenchymal Stem Cells Cell Biology equipment and supplies Frizzled Receptors Cell biology Tissue‐specific Stem Cells 030104 developmental biology medicine.anatomical_structure Molecular Medicine Stem cell 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cells (Dayton, Ohio) |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.3317 |
| Popis: | Human mesenchymal stem/stromal cells (hMSCs) have garnered enormous interest as a potential resource for cell‐based therapies. However, the molecular mechanisms regulating senescence in hMSCs remain unclear. To elucidate these mechanisms, we performed gene expression profiling to compare clonal immature MSCs exhibiting multipotency with less potent MSCs. We found that the transcription factor Frizzled 5 (FZD5) is expressed specifically in immature hMSCs. The FZD5 cell surface antigen was also highly expressed in the primary MSC fraction (LNGFR+THY‐1+) and cultured MSCs. Treatment of cells with the FZD5 ligand WNT5A promoted their proliferation. Upon FZD5 knockdown, hMSCs exhibited markedly attenuated proliferation and differentiation ability. The observed increase in the levels of senescence markers suggested that FZD5 knockdown promotes cellular senescence by regulating the noncanonical Wnt pathway. Conversely, FZD5 overexpression delayed cell cycle arrest during the continued culture of hMSCs. These results indicated that the intrinsic activation of FZD5 plays an essential role in negatively regulating senescence in hMSCs and suggested that controlling FZD5 signaling offers the potential to regulate hMSC quality and improve the efficacy of cell‐replacement therapies using hMSCs. Although mesenchymal stem/stromal cells (MSCs) are promising for cell therapy, long‐term culture leads to MSC senescence with reduced stem cell capacity. We showed that FZD5, which is specifically expressed in immature MSCs, can serve as a stemness indicator. Controlling FZD5 signaling may improve MSC quality and the outcomes of cell therapy. |
| Databáze: | OpenAIRE |
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