The manuscript by Prasai et al. presents a comprehensive systematic review and meta‑analysis of pre‑clinical (rodent) studies evaluating exosome‑based therapy for cutaneous wound repair. Following PRISMA and modified STAIR guidelines, the authors screened 3,064 records, ultimately including 51 studies (32 mouse, 19 rat) in the qualitative synthesis and 9 studies in the quantitative meta‑analysis. The review documents that exosome administration consistently improves wound closure rates, angiogenesis, collagen deposition, and overall healing across the three wound‑healing phases, with the strongest effect observed at 7 days post‑treatment (odds ratio 1.82, 95 % CI 0.69–2.95) and a comparable effect at 14 days (OR 2.29, 95 % CI 0.01–4.56). Exosomes are predominantly derived from mesenchymal stem cells, isolated mainly by ultracentrifugation, and characterized using a combination of western blot, TEM, and nanoparticle tracking. The cargo most frequently implicated in therapeutic benefit is micro‑RNA (e.g., miR‑21, miR‑126, miR‑20b), which modulates inflammation (M1→M2 macrophage polarization, PD‑L1), proliferation (fibroblast/keratinocyte AKT/HIF‑1α, Notch signaling), and angiogenesis (Wnt/β‑catenin, PI3K/AKT pathways). The authors calculate an inter‑quartile range for effective exosome protein dosing of 31.84 µg cm⁻², with an average reported dose of 83.76 µg cm⁻², highlighting the need for standardized dosing guidelines. Quality assessment reveals a mean STAIR score of ~5/10, indicating moderate methodological rigor but noting frequent omissions (temperature control, sample‑size calculations, reporting of excluded animals). The discussion emphasizes the heterogeneity of isolation/characterization protocols, the paucity of long‑term remodeling data, and calls for consensus standards to facilitate translation to clinical trials.
Topics
Systematic Review Framework for Pre‑clinical Exosome Studies
Application of PRISMA and modified STAIR guidelines to identify, screen, and assess rodent wound‑healing studies involving exosomes.
Quantitative Efficacy of Exosomes: Meta‑analysis Outcomes
Effect‑size synthesis showing improved wound closure at 7 days (OR 1.82) and 14 days (OR 2.29), forest‑plot visualizations, and funnel‑plot bias assessment.
Exosome Source, Isolation, and Characterization Landscape
Breakdown of cell origins (MSC ≈ 40 %, umbilical cord 10 %), isolation methods (ultracentrifugation 64 %, kits 18 %), and validation techniques (WB + TEM, NTA, flow cytometry) with marker prevalence (CD9/63/81, TSG101).
Therapeutic Dosing Guidance Derived from Pre‑clinical Data
Reported concentrations expressed as µg protein cm⁻², inter‑quartile range 31.84 µg cm⁻², mean 83.76 µg cm⁻², and discussion of variability due to culture conditions and isolation efficiency.
Molecular Cargo Driving Healing: miRNA‑Centric Mechanisms
Catalog of frequently reported miRNAs (miR‑21, miR‑126, miR‑20b, miR‑181c) and their phase‑specific actions: inflammation resolution, fibroblast/keratinocyte proliferation, angiogenesis via PI3K/AKT, Wnt/β‑catenin, and MMP/TIMP modulation.
Phase‑Specific Biological Effects of Exosomes
How exosomes modulate inflammation (M1→M2, PD‑L1), proliferation (AKT/HIF‑1α, Notch), angiogenesis (VEGF, Wnt), and remodeling (MMP/TIMP balance) across the three wound‑healing stages.
Quality Assessment and Methodological Gaps
STAIR‑based scoring (mean ≈ 5/10), common deficiencies (temperature reporting, sample‑size calculation, animal exclusion reporting), and impact on confidence in findings.
Limitations, Heterogeneity, and Future Standardization Needs
Discussion of inconsistent isolation/characterization, short follow‑up periods, limited clinical data, and the call for unified reporting standards to enable translational progress.