Therapeutic value of mesenchymal stem cell-derived extracellular vesicles in hypertrophic and keloid scars: a systematic review and meta-analysis

TL;DR

This study reviews preclinical evidence showing that mesenchymal stem cell-derived extracellular vesicles may help reduce scar formation in keloids and hypertrophic scars.

Contribution

The paper provides a meta-analysis of preclinical studies to evaluate the therapeutic potential of MSC-EVs in treating keloids and hypertrophic scars.

Findings

MSC-EVs significantly reduce the dimensions of hypertrophic scars and keloids in animal models.

MSC-EVs inhibit collagen deposition and suppress TGF-β1 and α-SMA expression in scar tissue.

MSC-EVs reduce fibroblast migration and proliferation, key factors in scar formation.

Abstract

Keloids and hypertrophic scars are pathological wound healing responses characterized by excessive scar tissue formation, presenting significant challenges to both patients and healthcare systems globally. Existing evidence demonstrates that mesenchymal stem cell–derived extracellular vesicles (MSC-EVs) can attenuate collagen deposition and contraction in scar tissue; however, their application in the treatment of hypertrophic scars and keloids remains largely at the preclinical stage. This systematic review aims to critically assess preclinical studies on the therapeutic efficacy of MSC-EVs in the management of keloids and hypertrophic scars. The review synthesizes findings from controlled and interventional studies, focusing on the use of MSC-EVs in animal models of these scars and their application in human subjects with raised scars following skin injury.

A total of 15 studies involving 253 animals were identified through a comprehensive search of the PubMed, Cochrane, Embase, MEDLINE Complete, Web of Science, CNKI, and Wanfang databases, covering the period from their inception to August 29, 2025. The aim was to evaluate the effects of MSC-EV therapy on keloids and hypertrophic scars through a meta-analysis of the standardized mean difference (SMD) in preclinical animal models. Meta-analyses were conducted using Stata 18 software.

Meta-analysis indicated that compared with the control group, MSC-Exos treatment group can significantly reduce. The dimensions of hypertrophic scars and keloids [(SMD) −2.78, 95% confidence interval (CI) −3.88–1.69)]. Also attenuate other outcomes, such as Collagen Type I [SMD = −4.39, 95%CI: −5.96–2.81], Collagen Type III [SMD = −5.19, 95%CI: −6.93–3.44], migration and proliferation of skin fibroblasts, and the expression of Transforming Growth Factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in scar tissue.

The meta-analysis supports the therapeutic potential of MSC-EVs in the treatment of keloids and hypertrophic scars, as demonstrated in preclinical animal models. MSC-EV therapy has been shown to downregulate the dimensions of hypertrophic scars and keloids, inhibit collagen deposition, and reduce migration and proliferation of skin fibroblasts. Additionally, MSC-EVs suppress the expression of TGF-β1 and α-SMA in scar tissue. These findings highlight MSC-EVs as a promising therapeutic approach for managing keloids and hypertrophic scars.

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