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Fibronectin and vitronectin alleviate adipose-derived stem cells senescence during long-term culture through the

Patcharapa Tragoonlugkana1, Chatchai Pruksapong2, Pawared Ontong3

  • 1Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon Sai 4, Salaya, Phutthamonthon, Nakhon Pathom, 73170, Thailand.

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Fibronectin (FN) and vitronectin (VN) surface coatings slow cellular senescence in adipose-derived stem cells (ADSCs). This enhances cell quality for regenerative medicine and cell therapies.

Keywords:
Adipose-derived stem cellsCell cultureCell therapyFibronectinGood manufacturing practiceReplicative senescenceVitronectin

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Area of Science:

  • Cell Biology
  • Regenerative Medicine
  • Biomaterials Science

Background:

  • Cellular senescence contributes to age-related degenerative diseases.
  • Two-dimensional cell culture induces replicative senescence, impacting cell therapy potential.
  • Adipose-derived stem cells (ADSCs) are crucial for cell therapy but susceptible to senescence during expansion.

Purpose of the Study:

  • To investigate the impact of fibronectin (FN) and vitronectin (VN) surface modification on ADSC characteristics during long-term expansion.
  • To evaluate the effect of these coatings on cellular senescence, adhesion, and proliferation.

Main Methods:

  • Long-term expansion of ADSCs cultured on surfaces coated with FN and VN.
  • Assessment of cell adhesion, proliferation, and senescence markers (SA-β-gal activity, p16, p21, p53 gene expression).
  • Analysis of integrin signaling pathways (PI3K/AKT) and MDM2-p53 interaction.

Main Results:

  • FN and VN coatings significantly enhanced ADSC adhesion and proliferation.
  • These coatings slowed cellular senescence, evidenced by reduced SA-β-gal activity and lower expression of senescence markers (p16, p21, p53).
  • Upregulation of integrins (α5, αv) and AKT signaling, leading to MDM2-mediated p53 degradation was observed. MDM2 inhibition increased senescence and inflammation.

Conclusions:

  • FN and VN surface modification effectively mitigates cellular senescence in expanded ADSCs.
  • This strategy improves ADSC quality for cell-based therapies by enhancing proliferation and delaying senescence.
  • Understanding these surface-cell interactions provides a practical approach for optimizing ADSC cultivation for therapeutic applications.