The efficacy and safety of autologous epidermal cell suspensions for re-epithelialization of skin lesions: A systematic review and meta-analysis of randomized trials

Abstract

Background: Successful usage of autologous skin cell suspension (ASCS) has been demonstrated in some clinical trials. However, its efficacy and safety have not been verified. This latest systematic review and meta-analysis aim to examine the effects of autologous epidermal cell suspensions in re-epithelialization of skin lesions.

Methods: Relevant articles were retrieved from PubMed, Embase, Cochrane Database, Web of Science, International Clinical Trials Registry Platform, China National Knowledge Infrastructureris, VIP Database for Chinese Technical Periodicals and Wanfang database. The primary output measure was the healing time, and the secondary outputs were effective rate, size of donor site for treatment, size of study treatment area, operation time, pain scores, repigmentation, complications, scar scale scores and satisfaction scores. Data were pooled and expressed as relative risk (RR), mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval (CI).

Results: Thirty-one studies were included in this systematic review and meta-analysis, with 914 patients who received autologous epidermal cell suspensions (treatment group) and 883 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced healing time (SMD = -0.86; 95% CI: -1.59-0.14; p = 0.02, I² = 95%), size of donar site for treatment (MD = -115.41; 95% CI: -128.74-102.09; p<0.001, I² = 89%), operation time (MD = 25.35; 95% CI: 23.42-27.29; p<0.001, I² = 100%), pain scores (SMD = -1.88; 95% CI: -2.86-0.90; p = 0.0002, I² = 89%) and complications (RR = 0.59; 95% CI: 0.36-0.96; p = 0.03, I² = 66%), as well as significantly increased effective rate (RR = 1.20; 95% CI: 1.01-1.42; p = 0.04, I² = 77%). There were no significant differences in the size of study treatment area, repigmentation, scar scale scores and satisfaction scores between the two groups.

Conclusion: Our meta-analysis showed that autologous epidermal cell suspensions is beneficial for re-epithelialization of skin lesions as they significantly reduce the healing time, size of donar site for treatment, operation time, pain scores and complications, as well as increased effective rate. However, this intervention has minimal impact on size of treatment area, repigmentation, scar scale scores and satisfaction scores.

Keywords: autologous epidermal cell suspensions; complications; healing time; meta‐analysis; repigmentation; skin lesion; ulcer; vitiligo; wound.

FIGURE 1

PRISMA diagram detailing the literature search and the study selection/exclusion process. PRISMA, preferred reporting items for systematic reviews and meta‐analyses; RCT, randomized controlled trials.

FIGURE 2

Risk of bias charts. (A) Risk of bias in the included studies; (B) Risk of bias summary for all included studies.

FIGURE 3

Forest plot and funnel plot of the meta‐analysis illustrating the overall weighted effect size of autologous epidermal cell suspensions versus control on the healing time. (A) Forest plot. The diamond symbol at the bottom of the forest plot represents the overall weighted estimate. Different colors (green, red, yellow) and symbols (“+”, “−”, “?”) to denote “low risk of bias”, “high risk of bias” and “unclear risk of bias”, respectively. (B) Funnel plot. The effect size “SMD” is shown on the abscissa, and the inverse of the standard error of the value of the effect size, SE (SMD), is shown on the ordinate. The dots in the figure are the individual studies included. SMD, standardized mean difference.

FIGURE 4

Forest plot of the meta‐analysis illustrating the overall weighted effect size of autologous epidermal cell suspensions versus control on the effective rate. The diamond symbol at the bottom of the forest plot represents the overall weighted estimate.

FIGURE 5

Forest plots of the meta‐analysis illustrating the overall weighted effect size of autologous epidermal cell suspensions versus control on the size of donor site for treatment, size of study treatment area, operation time and pain scores. (A) Size of donor site for treatment. (B) Size of study treatment area. (C) Operation time. (D) Pain scores.

FIGURE 6

Forest plots of the meta‐analysis illustrating the overall weighted effect size of autologous epidermal cell suspensions versus control on the repigmentation. (A) 90%–100% repigmentation. (B) 75%–85% repigmentation. (C) 50%–74% repigmentation. (D) <50% repigmentation.

FIGURE 7

Forest plot and funnel plot of the meta‐analysis illustrating the overall weighted effect size of autologous epidermal cell suspensions versus control on the complications. (A) Forest plot. The diamond symbol at the bottom of the forest plot represents the overall weighted estimate. Different colors (green, red, yellow) and symbols (“+”, “–”, “?”) to denote “low risk of bias”, “high risk of bias” and “unclear risk of bias”, respectively. (B) Funnel plot. The effect size ”RR" is shown on the abscissa, and the inverse of the standard error of the value of the effect size, SE (log[RR]), is shown on the ordinate. The dots in the figure are the individual studies included.

FIGURE 8

Forest plot of the subgroup analysis of the overall weighted effect size of autologous epidermal cell suspensions versus control on the different complications. The diamond symbol at the bottom of the forest plot represents the overall weighted estimate. Different colors (green, red, yellow) and symbols (“+”, “‐”, “?”) to denote “low risk of bias”, “high risk of bias” and “unclear risk of bias”, respectively.

FIGURE 9

Forest plot of the meta‐analysis illustrating the overall weighted effect size of autologous epidermal cell suspensions versus control on the scar scale scores. The diamond symbol at the bottom of the forest plot represents the overall weighted estimate.

FIGURE 10

Forest plot of the meta‐analysis illustrating the overall weighted effect size of autologous epidermal cell suspensions versus control on the satisfaction scores. The diamond symbol at the bottom of the forest plot represents the overall weighted estimate.