The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study

Abstract

Background: Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate.

Results: ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year.

Conclusions: ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components.

Trial registration: registered with Chictr.org.cn (ChiCTR2100051405).

Keywords: keratinocyte; melanocyte; single-cell sequencing; transplantation; vitiligo.

Graphical Abstract

Figure 1.

Trial profile.

Figure 2.

Patient characteristics.

Figure 3.

Therapeutic effects of ACEG and correlation analysis with different clinical factors. The correlation analysis of therapeutic effects with gender, age, disease type, lesion site, course of disease, and stable period.

Figure 4.

scRNA-seq analysis of vitiligo skin samples. (a) UMAP dimensionality reduction analysis of single-cell transcriptome sequencing. (b) Proportion of different cell subpopulations in the 4 samples. (c) Proportion of significantly increased cell subpopulations after ACEG treatment in different samples. (d) Results of Reactome and GO clustering analysis for MC1, KC_EDN1, and KC_HF subpopulations. (e) The CellChat analysis of interactions between MC1, KC_EDN1, and KC_HF. (f) The proportion differences of MC1, KC_EDN1, and KC_HF in the normal skin and lesional skin of patients with vitiligo based on published data.