Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the AKT/MDM2/P53 pathway
Issued Date
2024-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85196362309
Journal Title
Scientific Reports
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.14 No.1 (2024)
Suggested Citation
Tragoonlugkana P., Pruksapong C., Ontong P., Kamprom W., Supokawej A. Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the AKT/MDM2/P53 pathway. Scientific Reports Vol.14 No.1 (2024). doi:10.1038/s41598-024-65339-z Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/99037
Title
Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the AKT/MDM2/P53 pathway
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Abstract
Cellular senescence plays a role in the development of aging-associated degenerative diseases. Cell therapy is recognized as a candidate treatment for degenerative diseases. To achieve the goal of cell therapy, the quality and good characteristics of cells are concerned. Cell expansion relies on two-dimensional culture, which leads to replicative senescence of expanded cells. This study aimed to investigate the effect of cell culture surface modification using fibronectin (FN) and vitronectin (VN) in adipose-derived stem cells (ADSCs) during long-term expansion. Our results showed that ADSCs cultured in FN and VN coatings significantly enhanced adhesion, proliferation, and slow progression of cellular senescence as indicated by lower SA-β-gal activities and decreased expression levels of genes including p16, p21, and p53. The upregulation of integrin α5 and αv genes influences phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), and AKT proteins. FN and VN coatings upregulated AKT and MDM2 leading to p53 degradation. Additionally, MDM2 inhibition by Nutlin-3a markedly elevated p53 and p21 expression, increased cellular senescence, and induced the expression of inflammatory molecules including HMGB1 and IL-6. The understanding of FN and VN coating surface influencing ADSCs, especially senescence characteristics, offers a promising and practical point for the cultivation of ADSCs for future use in cell-based therapies.