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Background <p>Extracellular vesicles (EVs) are promising therapeutics for diseases associated with inflammation and tissue remodeling. However, a major limitation for the clinical translation of EV therapeutics is heterogeneity, which is donor dependent. In this study we sought to assess the physiochemical characteristics and therapeutic efficacy of tissue-derived EVs from different donors. Donor-dependent therapeutic effects of cell culture and biofluid-derived EVs have previously been shown, but remains largely unknown for tissue-derived EVs. We obtained EV-enriched samples from various sources of adipose tissue and examined their effect in reducing inflammation in a highly translational model of myocarditis.</p> Results <p>We demonstrate that the molecular composition of EVs varies depending on the donor and that therapeutic efficiency is donor-dependent even when controlling for age and sex.</p> Conclusions <p>Our findings indicate that further research is needed to identify critical donor characteristics that predict therapeutic ability of individual or pooled adipose tissue-derived EVs to reduce inflammation and fibrosis.</p>

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Donor-dependent heterogeneity in therapeutic effects of adipose tissue extracellular vesicles

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月26日

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  • Danielle J. Beetler,
  • Presley Giresi,
  • Vivian Xu,
  • Elizabeth J. McCabe,
  • Jessica J. Fliess,
  • Alayna M. Puls,
  • Matthew E. Auda,
  • Molly M. Watkins,
  • Sierra A. Walker,
  • Damian N. Di Florio,
  • Dalila Iannotta,
  • Emily R. Whelan,
  • Logan P. Macomb,
  • Kevin C. Keegan,
  • Angita Jain,
  • Varsini Balamurugan,
  • Sami Khatib,
  • Gabriel J. Weigel,
  • David J. Gorelov,
  • Anthony Pham,
  • Brandy H. Edenfield,
  • Leslie T. Cooper Jr.,
  • Houssam Farres,
  • Shane A. Shapiro,
  • Katelyn A. Bruno,
  • Joy Wolfram,
  • DeLisa Fairweather

摘要

Background

Extracellular vesicles (EVs) are promising therapeutics for diseases associated with inflammation and tissue remodeling. However, a major limitation for the clinical translation of EV therapeutics is heterogeneity, which is donor dependent. In this study we sought to assess the physiochemical characteristics and therapeutic efficacy of tissue-derived EVs from different donors. Donor-dependent therapeutic effects of cell culture and biofluid-derived EVs have previously been shown, but remains largely unknown for tissue-derived EVs. We obtained EV-enriched samples from various sources of adipose tissue and examined their effect in reducing inflammation in a highly translational model of myocarditis.

Results

We demonstrate that the molecular composition of EVs varies depending on the donor and that therapeutic efficiency is donor-dependent even when controlling for age and sex.

Conclusions

Our findings indicate that further research is needed to identify critical donor characteristics that predict therapeutic ability of individual or pooled adipose tissue-derived EVs to reduce inflammation and fibrosis.