Alginate-polylysine-alginate (APA) microencapsulated transgenic human amniotic epithelial cells ameliorate fibrosis in hypertrophic scars

Hypertrophic scar (HS) is a severe skin fibrosis. Transplanting stem cells carrying anti-fibrotic cytokine genes, like interferon-gamma (IFN-γ), is a novel therapeutic strategy. Human amniotic epithelial cells (hAECs) are ideal seed cells and gene vectors. Microencapsulation creates a favorable environment for transplanted cells. This study investigates the effect of alginate-polylysine-alginate (APA)-microencapsulated hAECs modified with IFN-γ on HS fibrosis. hAECs were isolated from human placentas and characterized. The full-length IFN-γ gene was cloned into the pcDNA3.1 vector to create the recombinant plasmid IFN-γ-pcDNA3.1. This plasmid was then transfected into hAECs, resulting in the generation of IFN-γ-modified hAECs (IFN-γ-hAECs). Subsequently, these IFN-γ-hAECs were microencapsulated with APA to produce APA-IFN-γ-hAECs. In vitro, the release of IFN-γ, as well as the cellular and metabolic activities, growth, proliferation, migration, apoptosis, and trans-differentiation were assessed using HS-derived fibroblasts. In vivo, the weight loss of HS xenografts, collagen fiber arrangement, tissue oxidative stress, and inflammatory response were evaluated using a nude mouse model that had been transplanted with human HS tissues. In vitro, APA-IFN-γ-hAECs exhibited significantly sustained and enhanced IFN-γ release, increased cellular vitality, and inhibited fibroblast growth, proliferation, migration, and trans-differentiation into myofibroblasts. APA-IFN-γ-hAECs also remarkably downregulated extracellular matrix (ECM) components and promoted apoptosis. In vivo, they significantly accelerated the weight reduction of HS xenografts, improved collagen fiber arrangement, and mitigated oxidative stress and inflammation. This study suggests that APA-microencapsulated IFN-γ-hAECs may have potential in alleviating HS fibrosis, offering a new direction for exploring effective clinical HS management strategies.