Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the AKT/MDM2/P53 pathway.
Sci Rep
; 14(1): 14242, 2024 06 20.
Article
em En
| MEDLINE
| ID: mdl-38902430
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-ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteína Supressora de Tumor p53
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Fibronectinas
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Senescência Celular
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Vitronectina
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Proteínas Proto-Oncogênicas c-mdm2
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Proteínas Proto-Oncogênicas c-akt
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Tailândia
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM