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

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; Houssam Farres; Shane A. Shapiro; Katelyn A. Bruno; Joy Wolfram; De Lisa Fairweather

doi:10.1186/s12964-025-02563-8

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

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 PhamBrandy H. Edenfield, Leslie T. Cooper, Houssam Farres, Shane A. Shapiro, Katelyn A. Bruno, Joy Wolfram, De Lisa Fairweather

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1 Scopus citations

Abstract

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.

Original language	English (US)
Article number	4
Pages (from-to)	4
Journal	Cell Communication and Signaling
Volume	24
Issue number	1
DOIs	https://doi.org/10.1186/s12964-025-02563-8
State	Published - Nov 26 2025

Keywords

Anti-inflammatory
Exosomes
Lipoaspirate
Microvesicles
Myocarditis
Tangential flow filtration
TLR4
Humans
Male
Inflammation
Extracellular Vesicles/metabolism
Animals
Adipose Tissue/metabolism
Myocarditis/therapy
Female
Mice
Tissue Donors

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1186/s12964-025-02563-8

Cite this

Beetler, D. J., Giresi, P., Xu, V., McCabe, E. J., Fliess, J. J., Puls, A. M., Auda, M. E., Watkins, M. M., Walker, S. A., Di Florio, D. N., Iannotta, D., Whelan, E. R., Macomb, L. P., Keegan, K. C., Jain, A., Balamurugan, V., Khatib, S., Weigel, G. J., Gorelov, D. J., ... Fairweather, D. L. (2025). Donor-dependent heterogeneity in therapeutic effects of adipose tissue extracellular vesicles. Cell Communication and Signaling, 24(1), 4. Article 4. https://doi.org/10.1186/s12964-025-02563-8

Beetler, DJ, Giresi, P, Xu, V, McCabe, EJ, Fliess, JJ, Puls, AM, Auda, ME, Watkins, MM, Walker, SA, Di Florio, DN, Iannotta, D, Whelan, ER, Macomb, LP, Keegan, KC, Jain, A, Balamurugan, V, Khatib, S, Weigel, GJ, Gorelov, DJ, Pham, A, Edenfield, BH, Cooper, LT, Farres, H, Shapiro, SA, Bruno, KA, Wolfram, J & Fairweather, DL 2025, 'Donor-dependent heterogeneity in therapeutic effects of adipose tissue extracellular vesicles', Cell Communication and Signaling, vol. 24, no. 1, 4, pp. 4. https://doi.org/10.1186/s12964-025-02563-8

@article{90c73501a5794707834fa2a66d49cee8,

title = "Donor-dependent heterogeneity in therapeutic effects of adipose tissue extracellular vesicles",

abstract = "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.",

keywords = "Anti-inflammatory, Exosomes, Lipoaspirate, Microvesicles, Myocarditis, Tangential flow filtration, TLR4, Humans, Male, Inflammation, Extracellular Vesicles/metabolism, Animals, Adipose Tissue/metabolism, Myocarditis/therapy, Female, Mice, Tissue Donors",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = nov,

day = "26",

doi = "10.1186/s12964-025-02563-8",

language = "English (US)",

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pages = "4",

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TY - JOUR

T1 - Donor-dependent heterogeneity in therapeutic effects of adipose tissue extracellular vesicles

AU - Beetler, Danielle J.

AU - Giresi, Presley

AU - Xu, Vivian

AU - McCabe, Elizabeth J.

AU - Fliess, Jessica J.

AU - Puls, Alayna M.

AU - Auda, Matthew E.

AU - Watkins, Molly M.

AU - Walker, Sierra A.

AU - Di Florio, Damian N.

AU - Iannotta, Dalila

AU - Whelan, Emily R.

AU - Macomb, Logan P.

AU - Keegan, Kevin C.

AU - Jain, Angita

AU - Balamurugan, Varsini

AU - Khatib, Sami

AU - Weigel, Gabriel J.

AU - Gorelov, David J.

AU - Pham, Anthony

AU - Edenfield, Brandy H.

AU - Cooper, Leslie T.

AU - Farres, Houssam

AU - Shapiro, Shane A.

AU - Bruno, Katelyn A.

AU - Wolfram, Joy

AU - Fairweather, De Lisa

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/11/26

Y1 - 2025/11/26

N2 - 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.

AB - 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.

KW - Anti-inflammatory

KW - Exosomes

KW - Lipoaspirate

KW - Microvesicles

KW - Myocarditis

KW - Tangential flow filtration

KW - TLR4

KW - Humans

KW - Male

KW - Inflammation

KW - Extracellular Vesicles/metabolism

KW - Animals

KW - Adipose Tissue/metabolism

KW - Myocarditis/therapy

KW - Female

KW - Mice

KW - Tissue Donors

UR - https://www.scopus.com/pages/publications/105026703677

UR - https://www.scopus.com/inward/citedby.url?scp=105026703677&partnerID=8YFLogxK

U2 - 10.1186/s12964-025-02563-8

DO - 10.1186/s12964-025-02563-8

M3 - Article

C2 - 41299530

AN - SCOPUS:105026703677

SN - 1478-811X

VL - 24

SP - 4

JO - Cell Communication and Signaling

JF - Cell Communication and Signaling

IS - 1

M1 - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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