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Publications

Journal Article Epublish

PubMed: 40826359 DOI: 10.1186/s12967-025-06930-4

Mechanism of action behind the pain-relief effects of extracellular vesicles in microfragmented adipose tissue: an in vitro and in vivo study.

J Transl Med 23(1):931

Authors: Francesco De Francesco, Letizia Ferroni, Ilaria Zanolla, Lucia Sileo, Maria Pia Cavaleri, Mario Fordellone, Letizia Senesi, Anna Maria Monachino, Elena Tremoli, Ilenia Pia Cappucci, Eduardo Maria Sommella, Massimo Bonora, Alfredo Ronca, Ugo D'Amora, Noemi De Cesare, Luca Lovatti, Michele Riccio, Ali Mobasheri, Paolo Pinton, Barbara Zavan

Affiliations

  • Department of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, 60126, Ancona, Italy.
  • Maria Cecilia Hospital, GVM Care & Research, 48033, Cotignola, Ravenna, Italy.
  • Department of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
  • Department of Mental, Physical Health and Preventive Medicine Campania University L.Vanvitelli, Caserta, Italy.
  • Dipartimento di Farmacia, Università Degli Studi di Salerno, Fisciano, Italy.
  • Department of Medical Sciences, Section of Experimental Medicine, Laboratory for Advanced Therapies (LTTA), University of Ferrara, and Technopole of Ferrara, Ferrara, Italy.
  • Institute of Polymers, Composites and Biomaterials - National Research Council (IPCB-CNR), 23900, Lecco, Italy.
  • Institute of Polymers, Composites and Biomaterials - National Research Council (IPCB-CNR), 80125, Naples, Italy.
  • Institute of Polymers, Composites and Biomaterials - National Research Council (IPCB-CNR), 80125, Naples, Italy.
  • Research Unit of Health Sciences and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland.
  • Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
  • World Health Organization Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Université de Liège, Liège, Belgium.
  • Department of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.

Abstract

BACKGROUND

Trapeziometacarpal osteoarthritis (TMC OA) is a prevalent and debilitating condition that impairs hand functionality and reduces quality of life. Current treatments including conservative measures such as splinting and anti-inflammatory medications, as well as surgical interventions often exhibit limited efficacy or involve invasive procedures. Novel therapeutic approaches are necessary to address the pain and functional limitations experienced by affected patients.

METHODS

This study investigates the potential of extracellular vesicles (EVs) derived from autologous microfragmented adipose tissue (aMAT) as a minimally invasive treatment for TMC OA. EVs were characterized using morphological, proteomic, and functional analyses, revealing their ability to modulate cellular processes through proteins associated with extracellular matrix organization, wound healing, and inflammation regulation.

RESULTS

Functional studies demonstrated that EVs modulate calcium signaling and mitochondrial activity, enhancing cellular bioenergetics and mitigating inflammation-induced dysfunction. In a clinical study with 25 patients diagnosed with TMC OA (Eaton Stage II), aMAT-derived EVs demonstrated significant benefits. Pain scores, measured by the numeric rating scale, improved substantially both at rest and during activity. Functional assessments, including the Michigan Hand Outcomes Questionnaire and Kapandji opposition test, showed enhanced hand performance over 12 months. Strength tests indicated marked improvements in pinch grip, with no adverse effects or disease progression observed radiographically.

CONCLUSIONS

The findings underscore the potential of aMAT-derived EVs as a novel, effective, and minimally invasive treatment for TMC OA, providing both pain relief and functional recovery. Further randomized trials are necessary to validate these results and investigate broader clinical applications.

TRIAL REGISTRATION

This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and adhered to all relevant national and institutional ethical guidelines for research involving human participants. Approval for the study was obtained from the Ethics Committee of Marche Region, protocol n. 154/2021. All participants provided written informed consent before enrollment in the study. They were informed about the study's purpose, procedures, potential risks, and their right to withdraw at any time without consequences. Informed Patient Consent Statement: Informed consent was obtained from all individual participants included in the study, following the guidelines of the Human Research Approval Committee protocol number 2/2019.

MeSH

Extracellular Vesicles, Pain, Biomedical Research, Therapeutics, Tissues, Adipose Tissue