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<p>Skeletal muscle-derived extracellular vesicles (SkM-EVs) are promising candidates for non-invasive, systemically delivered therapies, but their functional specificity relative to clinically advanced mesenchymal stem cell-derived EVs (MSC-EVs) remains unclear. We reanalyzed public miRNA-seq datasets of SkM-EVs and MSC-EVs and integrated validated miRNA–mRNA interactions to infer pathway-level repression potential of EV miRNA cargo. Two complementary approaches were used: a differential-expression-based relative evaluation with RBiomirGS, and an abundance-weighted absolute evaluation that converts miRNA profiles into gene-level Impact Scores followed by preranked KEGG enrichment. Despite their different formulations, both approaches converged on a shared pattern. SkM-EV miRNAs showed a predicted repression bias in FoxO, TGF-β and ErbB signaling pathways linked to muscle atrophy, metabolic homeostasis and pro-proliferative signaling. By contrast, MSC-EV miRNAs showed a predicted repression bias in immune signaling pathways. These source-dependent pathway signatures provide hypothesis-generating evidence that SkM-EVs may be better suited for muscle-, metabolic-, and cancer-related indications, whereas MSC-EVs may be more appropriate for immunomodulatory indications, pending experimental validation. Our miRNA–target-based framework provides a general strategy to benchmark EV sources at the pathway level directly from miRNA profiles.</p>

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Functional properties of skeletal myotube-derived extracellular vesicles based on microRNA profiles: a comparative analysis with mesenchymal stem cell-derived extracellular vesicles

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月5日

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  • Yudai Kawamoto,
  • Atomu Yamaguchi,
  • Xiaoqi Ma,
  • Yunfei Fu,
  • Qingcheng Guo,
  • Mikiko Uemura,
  • Hidemi Fujino,
  • Noriaki Maeshige

摘要

Skeletal muscle-derived extracellular vesicles (SkM-EVs) are promising candidates for non-invasive, systemically delivered therapies, but their functional specificity relative to clinically advanced mesenchymal stem cell-derived EVs (MSC-EVs) remains unclear. We reanalyzed public miRNA-seq datasets of SkM-EVs and MSC-EVs and integrated validated miRNA–mRNA interactions to infer pathway-level repression potential of EV miRNA cargo. Two complementary approaches were used: a differential-expression-based relative evaluation with RBiomirGS, and an abundance-weighted absolute evaluation that converts miRNA profiles into gene-level Impact Scores followed by preranked KEGG enrichment. Despite their different formulations, both approaches converged on a shared pattern. SkM-EV miRNAs showed a predicted repression bias in FoxO, TGF-β and ErbB signaling pathways linked to muscle atrophy, metabolic homeostasis and pro-proliferative signaling. By contrast, MSC-EV miRNAs showed a predicted repression bias in immune signaling pathways. These source-dependent pathway signatures provide hypothesis-generating evidence that SkM-EVs may be better suited for muscle-, metabolic-, and cancer-related indications, whereas MSC-EVs may be more appropriate for immunomodulatory indications, pending experimental validation. Our miRNA–target-based framework provides a general strategy to benchmark EV sources at the pathway level directly from miRNA profiles.