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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Integrative and Regenerative Pharmacology

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1635151

This article is part of the Research TopicMesenchymal Stem Cells and Derived Extracellular Vesicles as Next-Generation Biological Drugs for Tissue RegenerationView all 5 articles

Modulation of ASC-derived Extracellular Vesicles containing cargo that specifically enhances wound healing

Provisionally accepted
Jodi  GurneyJodi Gurney1*John  W LudlowJohn W Ludlow2Michael  J. Van KaneganMichael J. Van Kanegan1Robin  L SmithRobin L Smith1*
  • 1Exotropin, LLC, New York, United States
  • 2ZenBio, a BioIVT Company, Durham, United States

The final, formatted version of the article will be published soon.

We have developed a bioreactor-based production system for manufacturing Human Adipose Stromal Cell (ASC) extracellular vesicles (EVs), which includes exosomes, using a highly controlled and tunable environment that can modify the cargo of these nanovesicles. The patented innovation focuses on engineering novel pro-healing EVs with therapeutic activity and using a topical formulation to treat diabetic ulcers.Methods: To evaluate biological activity of tuned ASC EVs, functional activity assays were performed using human primary dermal fibroblast and keratinocyte culture models. Molecular and biochemical assays were used to assess cytokine regulation, collagen production and cell migration. Rodent wound healing models were used to assess therapeutic potential of modified exosomes. A Human volunteer case study was carried out with a consenting individual suffering from chronic diabetic ulcers.Results: Herein we demonstrate that our proprietary engineered ASC EVs, eXo 3 exosomes, contain a unique activity profile that reduces inflammatory cytokines, stimulates collagen production, as well as activates keratinocyte and fibroblast proliferation and migration. When formulated with an emollient and topically applied to an in vivo excisional wound model, tuned eXo 3 exosomes demonstrated enhanced wound closure, increased keratinization, collagen deposition, and overall improved recover rate. In a clinical case study addressing non-healing diabetic foot ulcers, conducted under informed consent, topical treatment with tuned eXo 3 exosomes formulated in a proprietary gel serum showed complete wound closure and dermal regeneration.Our current research efforts have developed an EV manufacturing system that can be directed to improve the healing capacity of ASC-derived EVs. We show enhanced wound healing and repair activity in vitro and in vivo. Our data supports the regenerative properties of exosomes and reinforces their strong therapeutic potential.

Keywords: Exosomes1, regenerative medicine2, wound healing3, Adipose-derived stromal/stem cells4, diabetic ulcer5, extracellular vesicles6, therapeutic vehicle7, Mesenchymal Stem Cells8

Received: 26 May 2025; Accepted: 07 Aug 2025.

Copyright: © 2025 Gurney, Ludlow, Van Kanegan and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jodi Gurney, Exotropin, LLC, New York, United States
Robin L Smith, Exotropin, LLC, New York, United States

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.