REVIEW article
Front. Vet. Sci.
Sec. Animal Reproduction - Theriogenology
This article is part of the Research TopicThe Role of Extracellular Vesicles in Animal ReproductionView all 4 articles
Extracellular Vesicles in Stem Cell-Based Gonadal Regeneration: Mechanisms, Therapeutic Potential, and Translational Challenges
Provisionally accepted
- Universidade de Marilia, Marília, Brazil
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Gonadal dysfunction resulting from conditions such as premature ovarian insufficiency, chemotherapy-induced damage, or genetic disorders often leads to infertility and hormone imbalance. Although assisted reproductive technologies and hormone replacement therapies mitigate clinical symptoms, they remain incapable of reinstating native gonadal architecture and physiological function. In recent years, stem cell-based therapies, particularly those employing mesenchymal stem cells (MSCs), have demonstrated regenerative potential. However, limitations including poor engraftment, potential tumorigenicity, and ethical concerns, have accelerated the paradigm shift toward extracellular vesicles (EVs) as a safer, cell-free alternative. EVs derived from MSCs are membrane-bound nanovesicles enriched with regulatory microRNAs, proteins, and lipids that exert potent paracrine effects. These vesicles modulate apoptosis, inflammation, fibrosis, and angiogenesis. MSC-EVs can restore folliculogenesis, support spermatogenesis, and normalize hormonal profiles in preclinical models of ovarian and testicular failure. Notably, EVs derived from adipose tissue, bone marrow, placenta, or amniotic membrane exhibit regenerative potential while mitigating the risks associated with live-cell transplantation. This review synthesizes current advances in MSC-EV-based therapies for gonadal regeneration, highlighting their integration into reproductive tissue engineering. Incorporating EVs into decellularized extracellular matrix scaffolds offers promising strategies for targeted tissue repair, extending their application in organoid systems for in vitro gametogenesis, disease modeling, and drug screening. Despite challenges related to EV heterogeneity, standardization of isolation, and delivery strategies, MSCs-derived EVs represent a transformative and ethically sound platform for restoring fertility and endocrine function.
Keywords: extracellular vesicles, Gonads, Regeneration, Regenerative Medicine, Stem Cell Therapy
Received: 11 Jun 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Flores Abuna, FORNARI LAURINDO, Barbalho and Miglino. 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: LUCAS FORNARI LAURINDO
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