Mesenchymal stem cells-derived small extracellular vesicles and apoptotic extracellular vesicles for wound healing and skin regeneration: a systematic review and meta-analysis of preclinical studies.

Abstract

Background: Studies examining the therapeutic potential of Mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) in wound healing and skin regeneration have progressed rapidly. Prior to considering clinical translation, a systematic and comprehensive understanding of these experimental details and the overall impact of MSC-EVs on skin regeneration is necessary.

Methods: 83 studies were identified in Web of Science, Embase, and PubMed that satisfied a set of prespecified inclusion criteria. A random effects meta-analysis was conducted for wound closure rate, scar width, blood vessel density and collagen deposition.

Conclusions: Our findings demonstrate clear potential of MSC-EVs to be developed as therapy for wound healing and skin regeneration both in diabetic and non-diabetic animal models. Moreover, subgroup analyses demonstrated that apoptotic small extracellular vesicles (ApoSEVs) showed better efficacy than apoptotic bodies (ApoBDs) and small extracellular vesicles (sEVs) in wound closure outcome and collagen deposition, while sEVs displayed better than ApoEVs in revascularization. Among frequently used routes of administration, subcutaneous injection displayed a greater improvement to wound closure, collagen deposition and revascularization as compared to dressing/covering. Among easier-access source of MSCs, ADSCs demonstrated the best effect in wound closure rate and collagen deposition, as compared, BMMSCs displayed better in revascularization. Additionally, high heterogeneity observed in collection conditions, separation methods, storage methods, modifications, treatment dose, administration route, and frequency of MSC-EVs underscores the urgent need for standardization in these areas, prior to clinical translation.

Protocol registration: PROSPERO CRD42024499172.