Hypoxia potentiated pro-angiogenic and anti-fibrotic effect of nanovesicles derived from human mesenchymal stem cells

초록

Skin acts as a frontline defense that protects against external invasion of pathogens and harmful substances. When the skin if injured, wound healing to reconstruct the skin is mainly supervised by fibroblasts. For optimal wound healing, proper neovascularization and reduced scar formation are essential factors that contribute to skin regeneration. In this context, various studies have examined the application of stem cells or stem cell-derived materials such as nanovesicles (NVs) in wound healing. In the present study, a hypoxic cell culture condition was used to engineer mesenchymal stem cells (MSCs) to generate NVs with enhanced angiogenic and anti-fibrotic efficacy. Hypoxic culture condition (2 % O2, 48 h) MSCs-derived NVs (H-NVs) showed more angiogenic and less pro-inflammatory factor expression compared to NVs derived from mesenchymal stem cell under normoxic culture condition (N-NVs). The H-NVs treatment showed upregulated angiogenesis with increased migration and proliferation of skin fibroblasts. Moreover, H-NVs treatment downregulated myofibroblast differentiation, which is critical for scar formation. In summary, this study confirmed that the use of a hypoxic cell culture condition can be a key factor enhancing the therapeutic efficacy of NVs in terms of effective angiogenesis and anti-fibrosis. © 2024 The Korean Society of Industrial and Engineering Chemistry

키워드