Role of Exosomes in Dermal Wound Healing: A Systematic Review

Abstract

Cell-based therapy imparts its therapeutic effects through soluble GFs and vesicular bodies such as exosomes. A systematic review with a meta-analysis of preclinical studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the modified Stroke Therapy Academic Industry Roundtable guidelines to identify exosomes as an archetype biological therapy for dermal wound healing and to provide guidelines for the concentrations to be used in preclinical studies. A total of 51 rodent studies were included in the systematic review and 9 were included in the meta-analysis section. Three independent reviewers cross-screened eligibility and selected studies for quality assessment from 3,064 published studies on exosomes and wound healing. The mean quality scores for all studies were 5.08 ± 0.752 and 5.11 ± 1.13 for systematic review and meta-analysis, respectively. Exosome effects were reported to have the highest efficacy at 7 days (OR = 1.82, 95% confidence interval = 0.69‒2.95) than at 14 days (OR = 2.29, 95% confidence interval = 0.01‒4.56) after administration. Exosomes were reported to regulate all phases of skin wound healing, mostly by the actions of circulating microRNA. The outcome of this review may be used to guide preclinical and clinical studies on the role of exosomes in wound healing.

Figure 1.

Flow diagram of the literature search, review, and selection of the studies analyzed for systematic review or meta-analysis. The workflow followed the PRISMA guidelines.

Figure 2.. Methodologies used to characterize exosomes.

Diagram showing different methods used to visualize and characterize exosomes. Most studies used Western blot in combination with microscopic analysis.

Figure 3.. Meta-analysis of the effects of exosomes in wound healing on day 7 after application.

a) Each effect size of EV across studies at 7 days post-application of exosomes. Forest plot showing a median effect size and 95% CI. b) Funnel plots for exosome applications in wound healing models displaying the distribution of researched study outcomes (dots) to estimate potential publication bias in 7 days of post-application studies. Note: data points for Xiong (2020) and Zhao (2020) at 3.88 and 3.87, are overlapping and are depicted as one data point.

Figure 4.. Meta-analysis of the effects of exosomes in wound healing on day 14 after application.

a) Each effect size of EV across studies at 14 days post-application of exosomes. Forest plot showing a median effect size and 95% CI. b) Funnel plots for exosome applications in wound healing models showed the distribution of researched study outcomes (dots) to estimate potential publication bias in 7 days post-application studies.

Figure 5.

Summary of bioactive contents of exosomes that are facilitating and accelerating wound healing; miRNA was the most common signaling molecule, followed by growth factors.