FN9-10ELP, an ECM-Mimetic Fusion Protein, Suppresses Etoposide-Induced Senescence in Human Mesenchymal Stem Cells

Background: Cellular senescence impairs the therapeutic potential of mesenchymal stem cells (MSCs), limiting their clinical applications. In this study, we aimed to eval-uate whether FN9-10ELP, a recombinant ECM-mimetic fusion protein composed of fi-bronectin type III domains 9 and 10 conjugated to elastin-like polypeptides, could sup-press senescence induced by the chemotherapeutic agent etoposide in hTMSCs. Methods: Senescence was induced in hTMSCs by treatment with 20μM etoposide. The anti-senescence effects of FN9-10ELP were evaluated by assessing cell viability (MTT assay), senescence-associated gene expression (qRT-PCR), nuclear morphology (DAPI staining), and SA-β-galactosidase activity. Results: FN9-10ELP treatment significantly enhanced cell viability and attenuated the mRNA expression of senescence-associated secretory phenotype (SASP) genes, in-cluding IL-6, IL8, and PAI-1. Furthermore, FN9-10ELP reduced etoposide-induced nu-clear enlargement and decreased the proportion of SA-β-gal-positive cells, indicating attenuation of the senescence phenotype. Conclusions: FN9-10ELP suppresses etoposide-induced senescence in hTMSCs by pre-serving cell viability and reducing the expression of SASP factors and morphological senescence markers. These findings highlight the potential of ECM-mimetic proteins such as FN9-10ELP as promising biomaterials in regenerative medicine and anti-aging therapies.