Preclinical efficacy of extracellular vesicle therapy in peripheral nerve injury: a comprehensive systematic review and network meta-analysis.
8 affiliations
- 1Cancer Epidemiology Research Center, AJA University of Medical Sciences, Tehran, Iran.
- 2Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- 3Toxicology Research Center, AJA University of Medical Sciences, Tehran, Iran.
- 4Medical Biotechnology Research Center, AJA University of Medical Sciences, PO box: 1411718541, Tehran, Iran.
- 5Anesthesiology Department, College of Health Profession and Medical Sciences, Barry University, Miami Shores, Florida, USA.
- 6Trauma Research Center, AJA University of Medical Sciences, PO box: 1411718541, Tehran, Iran. [email protected].
- 7Medical Biotechnology Research Center, AJA University of Medical Sciences, PO box: 1411718541, Tehran, Iran. [email protected].
- 8Infectious Disease Research Center, AJA University of Medical Sciences, Tehran, Iran. [email protected].
Abstract
Background
Peripheral nerve injuries (PNIs) result in significant motor and sensory deficits, with autologous nerve grafting as the gold standard but limited by donor morbidity and incomplete recovery. Extracellular vesicles (EVs) have emerged as a promising cell-free therapy, offering potent paracrine signaling, safety, and immunological compatibility. This study systematically evaluated the preclinical efficacy of EV-based therapies for PNI.Methods
A systematic review and network meta-analysis were conducted according to PRISMA guidelines, searching PubMed, Scopus, and Web of Science to July 1, 2025. Eligible in vivo studies investigated EVs from any cell source in animal PNI models, compared with controls, and reported functional, structural, electrophysiological, or sensory outcomes. Risk of bias was assessed using the CAMARADES checklist. Three hierarchical meta-analyses compared EVs, structural grafts, cellular therapies, and combination strategies. The primary endpoint was sciatic functional index (SFI), and secondary outcomes included muscle preservation, sensory recovery, and electrophysiology.Results
Thirty-five studies met inclusion, with 32 included in quantitative synthesis. EV therapy significantly improved SFI versus control (MD: 21.80; 95% CI 7.20-36.39; p = 0.0034), with greater effects in crush injuries and when combined with scaffolds, conduits, or autografts (up to MD: 54.41). Secondary outcomes showed improved gastrocnemius weight, muscle fiber area, nerve conduction velocity, and mechanical withdrawal thresholds. MSC-derived EVs, particularly scaffold-delivered, yielded the most consistent gains, while Schwann cell-derived EVs were effective as monotherapy. Mechanistically, EVs enhanced axonal growth, remyelination, angiogenesis, and M2 macrophage polarization while reducing inflammation.Conclusions
EV-based therapies significantly enhance functional, structural, and electrophysiological recovery in preclinical PNI models, with synergistic benefits when combined with structural supports. Standardization of EV production and delivery, and validation in clinically relevant models, are essential for translation into human therapy.
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BibTeX
@article{tavanaei2026preclinical,
title = {{Preclinical efficacy of extracellular vesicle therapy in peripheral nerve injury: a comprehensive systematic review and network meta-analysis.}},
author = {Roozbeh Tavanaei and Aryan Seraj and Alireza Alikhani and Mohsen Chamanara and Mahdi Ghorbani and Saeed Oraee-Yazdani and Amir Rashidian and Amir Nezami Asl and Reza Heidari},
journal = {Stem cell research \& therapy},
year = {2026},
month = aug,
doi = {10.1186/s13287-026-05217-9},
url = {https://europepmc.org/article/MED/42972587},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Preclinical efficacy of extracellular vesicle therapy in peripheral nerve injury: a comprehensive systematic review and network meta-analysis.
AU - Roozbeh Tavanaei
AU - Aryan Seraj
AU - Alireza Alikhani
AU - Mohsen Chamanara
AU - Mahdi Ghorbani
AU - Saeed Oraee-Yazdani
AU - Amir Rashidian
AU - Amir Nezami Asl
AU - Reza Heidari
PY - 2026
DA - 2026/08/06
JO - Stem cell research & therapy
DO - 10.1186/s13287-026-05217-9
UR - https://europepmc.org/article/MED/42972587
AB - Background Peripheral nerve injuries (PNIs) result in significant motor and sensory deficits, with autologous nerve grafting as the gold standard but limited by donor morbidity and incomplete recovery. Extracellular vesicles (EVs) have emerged as a promising cell-free therapy, offering potent paracrine signaling, safety, and immunological compatibility. This study systematically evaluated the preclinical efficacy of EV-based therapies for PNI.Methods A systematic review and network meta-analysis were conducted according to PRISMA guidelines, searching PubMed, Scopus, and Web of Science to July 1, 2025. Eligible in vivo studies investigated EVs from any cell source in animal PNI models, compared with controls, and reported functional, structural, electrophysiological, or sensory outcomes. Risk of bias was assessed using the CAMARADES checklist. Three hierarchical meta-analyses compared EVs, structural grafts, cellular therapies, and combination strategies. The primary endpoint was sciatic functional index (SFI), and secondary outcomes included muscle preservation, sensory recovery, and electrophysiology.Results Thirty-five studies met inclusion, with 32 included in quantitative synthesis. EV therapy significantly improved SFI versus control (MD: 21.80; 95% CI 7.20-36.39; p = 0.0034), with greater effects in crush injuries and when combined with scaffolds, conduits, or autografts (up to MD: 54.41). Secondary outcomes showed improved gastrocnemius weight, muscle fiber area, nerve conduction velocity, and mechanical withdrawal thresholds. MSC-derived EVs, particularly scaffold-delivered, yielded the most consistent gains, while Schwann cell-derived EVs were effective as monotherapy. Mechanistically, EVs enhanced axonal growth, remyelination, angiogenesis, and M2 macrophage polarization while reducing inflammation.Conclusions EV-based therapies significantly enhance functional, structural, and electrophysiological recovery in preclinical PNI models, with synergistic benefits when combined with structural supports. Standardization of EV production and delivery, and validation in clinically relevant models, are essential for translation into human therapy.
SN - 1757-6512
ER -