First pilot case-control interventional study using autologous extracellular vesicles to treat chronic venous ulcers unresponsive to conventional treatments
“…Similarly, Pomatto et al show the positive effect of EVs isolated from ATMSC-CM and BMMSC-CM on healing of diabetic ulcers in mice [14]. The newest clinical study must be highlighted, with excellent results published by Gibello et al that described the mechanism, safety, and validity of using EVs for the healing of chronic venous ulcers unresponsive to conventional treatments in humans [48]. These applications reduce the risk of an organism's reaction after the application of stem cells and their subsequent separation.…”
The aim of this study was to provide a beneficial treatment effect of mesenchymal stem cell products derived from the canine amniotic membrane (AM-MSC) on the complicated wound healing process in dogs. AM-MSCs were characterized in terms of morphology, phenotypic profile, and multilineage differentiation potential. The in vitro study of the effect of canine amniotic mesenchymal stem cell conditioned media (AMMSC-CM) on a primary skin fibroblast cell culture scratch assay showed a decrease in the measured scratch area of about 66.39% against the negative control (Dulbecco’s Modified Eagle’s Medium—32.55%) and the positive control (Dulbecco’s Modified Eagle’s Medium supplemented with FGF2, N2, B27, and EGF—82.077%) after 72 h treatment. In the experimental study, seven dogs with complicated nonhealing wounds were treated with a combination of antibiotics, NSAIDs, and local AMMSC-CM application. After 15 days of therapy, we observed a 98.47% reduction in the wound surface area as opposed to 57.135% in the control group treated by conventional therapy based on debridement of necrotic tissue, antibiotic therapy, pain management, and change of wound dressing.
“…Similarly, Pomatto et al show the positive effect of EVs isolated from ATMSC-CM and BMMSC-CM on healing of diabetic ulcers in mice [14]. The newest clinical study must be highlighted, with excellent results published by Gibello et al that described the mechanism, safety, and validity of using EVs for the healing of chronic venous ulcers unresponsive to conventional treatments in humans [48]. These applications reduce the risk of an organism's reaction after the application of stem cells and their subsequent separation.…”
The aim of this study was to provide a beneficial treatment effect of mesenchymal stem cell products derived from the canine amniotic membrane (AM-MSC) on the complicated wound healing process in dogs. AM-MSCs were characterized in terms of morphology, phenotypic profile, and multilineage differentiation potential. The in vitro study of the effect of canine amniotic mesenchymal stem cell conditioned media (AMMSC-CM) on a primary skin fibroblast cell culture scratch assay showed a decrease in the measured scratch area of about 66.39% against the negative control (Dulbecco’s Modified Eagle’s Medium—32.55%) and the positive control (Dulbecco’s Modified Eagle’s Medium supplemented with FGF2, N2, B27, and EGF—82.077%) after 72 h treatment. In the experimental study, seven dogs with complicated nonhealing wounds were treated with a combination of antibiotics, NSAIDs, and local AMMSC-CM application. After 15 days of therapy, we observed a 98.47% reduction in the wound surface area as opposed to 57.135% in the control group treated by conventional therapy based on debridement of necrotic tissue, antibiotic therapy, pain management, and change of wound dressing.
“…SC-EVs are formidable vehicles for facilitating healing and tissue regeneration in diabetic wounds, thus expecting to be potential candidates for treating diabetic wounds. 137 , 138 Figure 1 Skin structure and comparison of normal and diabetic wounds. The skin is composed of the epidermis, dermis, and subcutaneous layers.…”
Wound healing is a sophisticated and orderly process of cellular interactions in which the body restores tissue architecture and functionality following injury. Healing of chronic diabetic wounds is difficult due to impaired blood circulation, a reduced immune response, and disrupted cellular repair mechanisms, which are often associated with diabetes. Stem cell-derived extracellular vesicles (SC-EVs) hold the regenerative potential, encapsulating a diverse cargo of proteins, RNAs, and cytokines, presenting a safe, bioactivity, and less ethical issues than other treatments. SC-EVs orchestrate multiple regenerative processes by modulating cellular communication, increasing angiogenesis, and promoting the recruitment and differentiation of progenitor cells, thereby potentiating the reparative milieu for diabetic wound healing. Therefore, this review investigated the effects and mechanisms of EVs from various stem cells in diabetic wound healing, as well as their limitations and challenges. Continued exploration of SC-EVs has the potential to revolutionize diabetic wound care.
“…Previous studies have confirmed the therapeutic efficacy of MSC-derived exosomes in addressing challenging wound-healing cases [ 14 , 15 ]. In a clinical study published in 2023[ 16 ], notable advancements were observed in the treatment of chronic venous ulcers that were unresponsive to conventional therapies. The study demonstrated enhanced therapeutic outcomes through the utilization of exosomes derived from the patient’s autologous serum.…”
Chronic trauma in diabetes is a leading cause of disability and mortality. Exosomes show promise in tissue regeneration. This study investigates the role of exosomes derived from adipose stem cells (ADSC-Exos) in angiogenesis. MiRNA-seq analysis revealed significant changes in 47 genes in human umbilical vein endothelial cells (HUVECs) treated with ADSC-Exos, with miR-146a-5p highly expressed. MiR-146a-5p mimics enhanced the pro-angiogenic effects of ADSC-Exos, while inhibitors had the opposite effect. JAZF1 was identified as a direct downstream target of miR-146a-5p through bioinformatics, qRT-PCR, and dual luciferase assay. Overexpress of JAZF1 resulted in decreased proliferation, migration, and angiogenic capacity of HUVECs, and reduced VEGFA expression. This study proposes that ADSC-Exos regulate angiogenesis partly via the miR-146a-5p/JAZF1 axis.
Graphical Abstract
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