Extracellular Vesicles From a Three-Dimensional Culture of Perivascular Cells Accelerate Skin Wound Healing in a Rat

Background: Soluble proteins and extracellular vesicles (EVs) are crucial wound repair mediators in cell-based therapy. Previous studies reported that EVs of perivascular cells stimulated migration and proliferation of cell types involved in the dermatological wound healing process. However, these studies only show effects of EVs from perivascular cells (PVCs) for in vitro models. Methods: EVs were collected from 3D-cultured PVC (PVC-3D-EV) and compared with EVs from 2D-culture PVC (PVC-2D-EV) to investigate effects on wound contraction, angiogenesis, activation of myofibroblast, and collagen deposition. Results: PVC-3D-EV was significantly improved in terms of wound contraction compared with PVC-2D-EV and the control. Activation of myofibroblast and collagen deposition in a rat skin wound model was significantly stimulated by PVC-3D-EV. In addition, angiogenesis and vascular endothelial growth factor expression were also highly stimulated by PVC-3D-EV. These results suggest that PVC-3D-EV was regulated in granulation tissue formation, angiogenesis, and wound contraction in healing of a rat skin wound. These results indicate a pivotal role of PVC-3D-EV in wound healing through multiple mechanisms. Conclusions: 3D-culture using a polystyrene scaffold is demonstrated to be a better system for providing better physiological conditions than the 2D-culture system, and EVs from 3D-cultured PVC could be a promising option for healing skin wound. No Level Assigned: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.