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Replicative senescence in amniotic fluid-derived mesenchymal stem cells and its impact on their immunomodulatory

Elham Zare1,2, Elham Sadat Hosseini3, Faezeh Sadat Azad2

  • 1Medical Genetics and Molecular Medicine Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Histochemistry and Cell Biology
|March 5, 2025
PubMed

Insights

Replicative senescence does not significantly impair the immunomodulatory properties of amniotic fluid-derived mesenchymal stem cells (AF-MSCs). Senescent AF-MSCs retain therapeutic potential, showing resilience in key immune gene expression despite prolonged culture.

Area of Science:

  • Stem Cell Biology
  • Immunology
  • Regenerative Medicine

Background:

  • Mesenchymal stem cells (MSCs) are crucial for regenerative medicine but their clinical use is limited by replicative senescence during in vitro expansion.
  • The effect of senescence on the immunomodulatory capacity of MSCs, particularly those derived from amniotic fluid (AF-MSCs), is not well understood.

Purpose of the Study:

  • To investigate the impact of replicative senescence on the immunomodulatory gene expression of AF-MSCs.
  • To assess the differentiation potential and immunomodulatory stability of AF-MSCs after prolonged culture and cryopreservation.

Main Methods:

  • AF-MSCs were derived from first-trimester amniotic fluid and characterized by flow cytometry.
  • Osteogenic and adipogenic differentiation potentials were evaluated.
  • Immunoregulatory gene expression (TGFβ, IL-10, IDO, VCAM-1, FASL, IL-6, COX1, HLA-G) was compared between proliferative and senescent AF-MSCs.
  • Cell proliferation markers (FOXM1, B-MYB) were assessed.

Main Results:

  • Senescent AF-MSCs maintained adipogenic differentiation capacity after cryopreservation.
  • Key immunomodulatory genes (TGFβ, IL-10, IDO, VCAM-1) showed no significant difference between proliferative and senescent cells.
  • Senescent cells exhibited downregulation of FASL and upregulation of IL-6, COX1, and HLA-G.
  • Cell proliferation markers FOXM1 and B-MYB were significantly downregulated in senescent cells.

Conclusions:

  • AF-MSCs demonstrate resilience in their immunomodulatory properties despite replicative senescence.
  • Senescence does not abrogate the potential therapeutic applications of AF-MSCs.
  • These findings support the use of AF-MSCs in clinical settings, even after extended in vitro culture.
Keywords:
Amniotic fluidExtraembryonic tissuesImmunomodulationMesenchymal stem cellsReplicative senescence

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