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<p>Mesenchymal stem cells (MSCs) exert immunomodulatory and regenerative effects primarily through their secretome, which comprises cytokines, growth factors, and extracellular vesicles. Although prolonged in vitro expansion has been reported to induce replicative senescence and alter MSC function, the functional consequences of passage-dependent changes in the MSC secretome remain incompletely characterized. In this study, we performed an integrated comparison of early- and late-passage MSC secretomes using THP-1 monocytic cells as an in vitro model to evaluate immunomodulatory and migratory responses. MSCs were characterized based on immunophenotype, proliferative capacity, and senescence-associated β-galactosidase activity. The biological effects of MSC secretomes on THP-1 cell viability, migration, and inflammatory responses were evaluated using MTT assays, chemotaxis assays, quantitative PCR, and ELISA. Early-passage MSC secretomes (EP-MSC-S) enhanced THP-1 cell viability, increased the expression of anti-inflammatory cytokines (IL-10 and TGF-β1), and reduced the transcript levels of pro-inflammatory mediators, including NF-κB, IL-1β, IL-6, and TNF-α. In contrast, late-passage MSC secretomes (LP-MSC-S) were associated with increased pro-inflammatory gene expression, enhanced migratory activity, and upregulation of CXCR4 and VEGF transcripts in THP-1 cells. Cytokine array profiling further demonstrated higher signal intensities of pro-inflammatory and chemotactic cytokines, including IL-1β, MCP-1, and MCP-2, in LP-MSC-S, whereas EP-MSC-S exhibited higher signal intensities of anti-inflammatory cytokines such as IL-4 and IL-13. Collectively, these findings provide functional evidence that MSC passage number is associated with coordinated changes in secretome composition and downstream immune and migratory responses in vitro. This study is limited by the use of an in vitro model, MSCs derived from a single donor, and gene-level pathway analysis without protein-level validation. Therefore, the findings should be interpreted as preliminary mechanistic associations that warrant further validation in multi-donor and in vivo models before translational applications can be considered.</p>

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Passage-Dependent Shifts in the Immunomodulatory and Migratory Properties of Mesenchymal Stem Cell Secretomes in THP-1 Monocytic Cells

  • 期刊论文

  • 发表日期：

    2026年5月6日

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  • Yanaphat Pleungtuk,
  • Amorn Pangjantuk,
  • Nipha Chaicharoenaudomrung,
  • Areechun Sotthibundhu,
  • Phongsakorn Chueaphromsri,
  • Phongsakorn Kunhorm,
  • Parinya Noisa

摘要

Mesenchymal stem cells (MSCs) exert immunomodulatory and regenerative effects primarily through their secretome, which comprises cytokines, growth factors, and extracellular vesicles. Although prolonged in vitro expansion has been reported to induce replicative senescence and alter MSC function, the functional consequences of passage-dependent changes in the MSC secretome remain incompletely characterized. In this study, we performed an integrated comparison of early- and late-passage MSC secretomes using THP-1 monocytic cells as an in vitro model to evaluate immunomodulatory and migratory responses. MSCs were characterized based on immunophenotype, proliferative capacity, and senescence-associated β-galactosidase activity. The biological effects of MSC secretomes on THP-1 cell viability, migration, and inflammatory responses were evaluated using MTT assays, chemotaxis assays, quantitative PCR, and ELISA. Early-passage MSC secretomes (EP-MSC-S) enhanced THP-1 cell viability, increased the expression of anti-inflammatory cytokines (IL-10 and TGF-β1), and reduced the transcript levels of pro-inflammatory mediators, including NF-κB, IL-1β, IL-6, and TNF-α. In contrast, late-passage MSC secretomes (LP-MSC-S) were associated with increased pro-inflammatory gene expression, enhanced migratory activity, and upregulation of CXCR4 and VEGF transcripts in THP-1 cells. Cytokine array profiling further demonstrated higher signal intensities of pro-inflammatory and chemotactic cytokines, including IL-1β, MCP-1, and MCP-2, in LP-MSC-S, whereas EP-MSC-S exhibited higher signal intensities of anti-inflammatory cytokines such as IL-4 and IL-13. Collectively, these findings provide functional evidence that MSC passage number is associated with coordinated changes in secretome composition and downstream immune and migratory responses in vitro. This study is limited by the use of an in vitro model, MSCs derived from a single donor, and gene-level pathway analysis without protein-level validation. Therefore, the findings should be interpreted as preliminary mechanistic associations that warrant further validation in multi-donor and in vivo models before translational applications can be considered.