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<p>Mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) are promising therapies across cardiovascular, inflammatory, metabolic, and neurodegenerative diseases. Metabolomics has revealed how MSCs/EVs reshape host metabolism, but current studies remain fragmented, small, and largely descriptive. Synthesizing evidence across disease models, we identify conserved metabolic checkpoints, succinate and α-ketoglutarate in the TCA cycle, acylcarnitines in fatty acid β-oxidation, and glutathione in redox balance, as recurrent targets linked to therapeutic benefit. Distinct signatures, including polyamine metabolism, bile acid–FXR/TGR5 signaling, and neurotransmitter regulation, provide disease-specific insights. Yet, most studies lack validation and reproducibility, limiting clinical translation. Progress requires larger datasets, targeted assays, integration into randomized trials, and GMP-aligned pipelines. We propose a Metabolomics-Derived MSC Potency Index, a standardized metabolite panel benchmarked against functional assays, as a framework for therapeutic readiness. This approach positions metabolomics not as a descriptive tool but as a translational benchmark guiding MSC/EV therapy development.</p> Graphical abstract <p></p>

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Metabolomics-guided Mechanisms of Mesenchymal Stromal Cell and Exosome Therapies in Chronic Diseases

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月6日

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  • Asma Ismail Mahmod,
  • Kayatri Govindaraju,
  • Yogeswaran Lokanathan,
  • Nur Akmarina,
  • B. M. Said,
  • Baharudin Ibrahim

摘要

Mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) are promising therapies across cardiovascular, inflammatory, metabolic, and neurodegenerative diseases. Metabolomics has revealed how MSCs/EVs reshape host metabolism, but current studies remain fragmented, small, and largely descriptive. Synthesizing evidence across disease models, we identify conserved metabolic checkpoints, succinate and α-ketoglutarate in the TCA cycle, acylcarnitines in fatty acid β-oxidation, and glutathione in redox balance, as recurrent targets linked to therapeutic benefit. Distinct signatures, including polyamine metabolism, bile acid–FXR/TGR5 signaling, and neurotransmitter regulation, provide disease-specific insights. Yet, most studies lack validation and reproducibility, limiting clinical translation. Progress requires larger datasets, targeted assays, integration into randomized trials, and GMP-aligned pipelines. We propose a Metabolomics-Derived MSC Potency Index, a standardized metabolite panel benchmarked against functional assays, as a framework for therapeutic readiness. This approach positions metabolomics not as a descriptive tool but as a translational benchmark guiding MSC/EV therapy development.

Graphical abstract