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Stem Cell-Based and Stem Cell-Related Regenerative Therapies for Pure Venous Ulcers: A Systematic Review

In brief

Stem cell spray speeds venous ulcer healing about ten times faster

A small double-blind trial of autologous bone-marrow mesenchymal stem cells delivered in a fibrin spray showed roughly a ten-fold increase in linear healing compared with saline or fibrin alone. Similar benefit was seen with hair-follicle grafts, which cut ulcer size by three-quarters versus one-third in controls. Results are promising but based on only 43 patients, diverse methods and limited safety data, so larger trials are needed.

Journal
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society (Q1)
Published
1 January 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Baiqiang Zhang, Jinghe Zhu, Sijing Wang, Yang Li, Yingfeng Wu
PMID
42683999
DOI
10.1111/wrr.70207

Why clinicians should know about it

  • Picked for Dermatology (top studies of the week, 6 September 2026): Stem cell therapy for venous ulcers, not dermatology focus

Abstract

Previous systematic reviews of stem cell-based therapies for lower limb ulcers have largely focused on arterial, diabetic or mixed-aetiology ulcers, while evidence in strictly defined pure venous ulcers remains scarce. This systematic review evaluated the efficacy and safety of stem cell-based and stem cell-related regenerative therapies for pure venous ulcers. PubMed, Embase, Web of Science and the Cochrane Library were searched up to February 2026 for comparative clinical studies. Studies involving arterial, diabetic, mixed or non-venous ulcers, non-comparative designs or insufficiently extractable data were excluded. Three studies involving 43 patients were included, comprising two randomised controlled trials and one non-randomised comparative study. Interventions included autologous bone marrow-derived mesenchymal stem cells in fibrin spray, hair follicle-containing punch grafts and antlerogenic stem cell extract. In one randomised double-blind pilot trial, mesenchymal stem cells in fibrin spray accelerated linear healing by approximately 10-fold compared with saline spray and fibrin spray alone (p < 0.01). Another randomised trial found greater ulcer area reduction at 18 weeks in hair follicle-treated areas than in control areas (75.15% [SD 23.03] vs. 33.07% [SD 46.17], p = 0.002). The non-randomised study reported significant improvements in wound area, circumference and healing-related indices, although Ki-67 expression did not differ significantly. No major treatment-related safety concerns were reported, although adverse-event data were limited. Current evidence suggests potential benefit, but findings remain preliminary because of small samples, heterogeneous interventions and variable outcome definitions. Larger standardised studies are needed. Trial Registration: CRD420261304878.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.