Mesenchymal Stem Cell Extracellular Vesicles from Tissue-Mimetic System Enhance Epidermal Regeneration via Formation of Migratory Cell Sheets

• DOI: 10.1007/s13770-023-00565-6
• Publication Date: 2023-07-29T10:01:56Z
• Authors: Jacob G. Hodge; Jennifer L. Robinson; Adam J. Mellott
• Keywords: Extracellular vesicles; Exosome

Abstract Background The secretome of adipose-derived mesenchymal stem cells (ASCs) offers a unique approach to understanding and treating wounds, including the critical process epidermal regeneration orchestrated by keratinocytes. However, 2D culture techniques drastically alter secretory dynamics ASCs, which has led ambiguity in secreted compounds (e.g., growth factors, exosomes, reactive oxygen species) may be driving epithelialization. Methods A novel tissue-mimetic 3D hydrogel system was utilized enhance retainment more regenerative ASC phenotype highlight functional differences between 3D. Subsequently, ASC-secretome stratified molecular weight presence/absence extracellular vesicles (EVs). fractions were then evaluated assess for capacity augment specific keratinocyte activities. Results Culture ASCs within enhanced protein secretion ~ 50%, exclusively coming from > 100 kDa fraction. ability modulate epithelialization functions, migration, proliferation, differentiation, morphology, resided “> kDa” fraction, with providing greatest improvement. EV two-fold exhibited dose-dependent effects on regeneration. Notably, ASC-EVs induced morphological changes keratinocytes reminiscent native regeneration, formation cell sheets. only 3D-EVs promoted collective sheet migration an epithelial-to-mesenchymal-like transition keratinocytes, whereas 2D-EVs contained anti-migratory stimulus. Conclusion This study demonstrates how environment is influencing capabilities. Additionally, role EVs modulating revealed their translatability future clinical therapies discussed.