Abstract
Mesenchymal stem cells are an attractive cell type for cytotherapy in wound healing. The authors recently developed a novel, adipose-tissue-derived, injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) for stem cell therapy. This study was designed to assess the therapeutic effects of ECM/SVF-gel on wound healing and potential mechanisms. ECM/SVF-gel was prepared for use in nude mouse excisional wound healing model. An SVF cell suspension and phosphate-buffered saline injection served as the control. The expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and monocyte chemotactic protein-1 (MCP-1) in ECM/SVF-gel were analyzed at different time points. Angiogenesis (tube formation) assays of ECM/SVF-gel extracts were evaluated, and vessels density in skin was determined. The ECM/SVF-gel extract promoted tube formation in vitro and increased the expression of the angiogenic factors VEGF and bFGF compared with those in the control. The expression of the inflammatory chemoattractant MCP-1 was high in ECM/SVF-gel at the early stage and decreased sharply during the late stage of wound healing. The potent angiogenic effects exerted by ECM/SVF-gel may contribute to the improvement of wound healing, and these effects could be related to the enhanced inflammatory response in ECM/SVF-gel during the early stage of wound healing.
Highlights
Wound healing is a highly complex process that remains a major challenge in modern medicine
extracellular matrix (ECM)/stromal vascular fraction (SVF)-gel and fresh adipose tissues were evaluated by Scanning Electron Microscopy (SEM)
In vivo degradation of the ECM may release growth factors from the scaffold and produce degradation products, and these peptides have chemoattractant effects on endothelial cells both in vivo and in vitro [57]. These protective effects of the ECM component in ECM/SVF-gel may contribute to the enhanced angiogenic response and final vascularization during the wound healing process
Summary
Wound healing is a highly complex process that remains a major challenge in modern medicine. Mesenchymal stem cells- (MSCs-) based cytotherapy is an attractive approach in wound healing due to the differentiation potential, immunomodulating properties, and paracrine effects of MSCs [2,3,4,5]. In most studies, ASCs suspensions are injected separately without the protection of extracellular matrix (ECM) components, leading to rapid elimination of ASCs by the immune system and subsequent poor cell retention at recipient sites [8,9,10]. All of these factors weaken the therapeutic effects and applications of ASCs-based cytotherapy
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