Impact of Smoking on the Efficacy of Human Autologous Oral Mucosal Epithelial Cell Sheet Transplantation for Treating Limbal Stem Cell Deficiency

Limbal stem cell deficiency (LSCD) results from the loss or dysfunction of limbal stem cells, posing a significant challenge due to limited treatment options. Autologous oral mucosal epithelial cell (OMEC) sheet transplantation is an innovative therapy, but its effectiveness in smokers remains unclear. This study aims to investigate the impact of smoking on the efficacy of autologous OMEC sheet transplantation for LSCD and explores how acrolein, a major cigarette smoke component, affects the biological properties of these cells. This retrospective cohort study included 13 LSCD patients (13 eyes), divided into never smokers (seven eyes) and smokers (six eyes), all of whom received autologous OMEC sheet transplantation. The study compared colony-forming abilities and sheet thickness between the groups, assessed corneal epithelial repair postoperatively, and conducted in vitro experiments treating human OMECs (hOMECs) with acrolein. Evaluations focused on colony-forming ability, stem cell marker protein P63 expression, and the secretion of repair factors (transforming growth factor-beta [TGF-β], basic fibroblast growth factor [bFGF], and hepatocyte growth factor [HGF]) as well as the wound healing potential in human corneal epithelial cells. Postoperative results showed significant improvements in corneal epithelial defects, neovascularization, and best visual acuity in never smokers. However, adhesions recurred in both groups, with earlier recurrence in smokers. In vitro, acrolein significantly inhibited the proliferation of OMECs, reduced P63 expression, and decreased the secretion of TGF-β and HGF, though bFGF levels remained unchanged, impairing wound healing in scratched corneal epithelial cells. Smoking adversely affects the efficacy of autologous OMEC transplantation for LSCD, with acrolein as a potential key factor. Future research should focus on understanding the mechanisms by which smoking impacts OMECs and developing improved therapeutic strategies for smokers with LSCD. <b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT03015779.