Scholarlink

Background <p>Human mesenchymal stromal cells (hMSCs) remain the most clinically advanced adult stem cell source; however, their therapeutic potential is limited by rapid replicative senescence during ex vivo expansion. Replicative senescence in hMSCs is characterized by cell cycle arrest, acquisition of senescence-associated β-galactosidase (SA-β-Gal) activity, and secretion of the senescence-associated secretory phenotype (SASP) factors.</p> Methods <p>We investigated whether conditioned medium derived from human extended pluripotent stem cells (hEPSCs), which possess both embryonic and extra-embryonic developmental potential beyond that of conventional embryonic stem cells (hESCs), could attenuate replicative senescence in human Wharton’s Jelly-derived MSCs (WJMSCs). Using sequential ultrafiltration (10&#xa0;kDa and 3&#xa0;kDa) followed by liquid chromatography-tandem mass spectrometry, we identified several proteins from hEPSC-conditioned medium. We then tested the combination of S100A9/GAPDH/S100A8 proteins for their effects on doxorubicin (DOXO)-induced and replicative senescence.</p> Result <p>hEPSC-conditioned medium markedly attenuated replicative senescence in hMSCs. Notably, the combination of S100A9/GAPDH/S100A8 proteins not only mitigated doxorubicin-induced senescence but also counteracted replicative senescence, as evidenced by a significant reduction in SA-β-Gal-positive cells and downregulated mRNA expression of senescence-associated genes, including p16, p21, and the SASP factor IL-6. Furthermore, EdU incorporation assays revealed significantly enhanced proliferative capacity following treatment.</p> Conclusions <p>Collectively, our findings establish a defined protein combination (S100A9/GAPDH/S100A8) that counteracts both replicative and stress-induced senescence, offering a novel, cell-free strategy to enhance the clinical utility of WJMSCs.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Secreted protein combination GAPDH/S100A8/S100A9 from human expanded potential stem cells counteracts mesenchymal stromal cell senescence

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月30日

查看全文
  • Qingcai Feng,
  • Qianwen Pang,
  • Hongyu Lu,
  • Zijing Liu,
  • Zhancheng Lin,
  • Zhou Songyang,
  • Feng Liu,
  • Guang Shi

摘要

Background

Human mesenchymal stromal cells (hMSCs) remain the most clinically advanced adult stem cell source; however, their therapeutic potential is limited by rapid replicative senescence during ex vivo expansion. Replicative senescence in hMSCs is characterized by cell cycle arrest, acquisition of senescence-associated β-galactosidase (SA-β-Gal) activity, and secretion of the senescence-associated secretory phenotype (SASP) factors.

Methods

We investigated whether conditioned medium derived from human extended pluripotent stem cells (hEPSCs), which possess both embryonic and extra-embryonic developmental potential beyond that of conventional embryonic stem cells (hESCs), could attenuate replicative senescence in human Wharton’s Jelly-derived MSCs (WJMSCs). Using sequential ultrafiltration (10 kDa and 3 kDa) followed by liquid chromatography-tandem mass spectrometry, we identified several proteins from hEPSC-conditioned medium. We then tested the combination of S100A9/GAPDH/S100A8 proteins for their effects on doxorubicin (DOXO)-induced and replicative senescence.

Result

hEPSC-conditioned medium markedly attenuated replicative senescence in hMSCs. Notably, the combination of S100A9/GAPDH/S100A8 proteins not only mitigated doxorubicin-induced senescence but also counteracted replicative senescence, as evidenced by a significant reduction in SA-β-Gal-positive cells and downregulated mRNA expression of senescence-associated genes, including p16, p21, and the SASP factor IL-6. Furthermore, EdU incorporation assays revealed significantly enhanced proliferative capacity following treatment.

Conclusions

Collectively, our findings establish a defined protein combination (S100A9/GAPDH/S100A8) that counteracts both replicative and stress-induced senescence, offering a novel, cell-free strategy to enhance the clinical utility of WJMSCs.