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

Tianhui Zhai,W. Tang,Pengchao Liu,Yakun Liang,Zhihong Ma,Leiqiang Fan

Published 2026 in Frontiers in Cell and Developmental Biology

ABSTRACT

Background 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. Methods 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. Results 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. Conclusion 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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