Secretome from human adipose-derived mesenchymal stem cells promotes blood vessel formation and pericyte coverage in experimental skin repair

Abstract

Human adipose tissue-derived stem cells (hASC) secretome display various therapeutically relevant effects in regenerative medicine, such as induction of angiogenesis and tissue repair. The benefits of hASC secretome are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in host cells. However, the composition and the innate characteristics of hASC secretome can be highly variable depending on the culture conditions. Here, we evaluated the combined effect of serum-free media and hypoxia preconditioning on the hASCs secretome composition and biological effects on angiogenesis and wound healing. The hASCs were cultured in serum-free media under normoxic (NCM) or hypoxic (HCM) preconditioning. The proteomic profile showed that pro- and anti-antiangiogenic factors were detected in NCM and HCM secretomes. In vitro studies demonstrated that hASCs secretomes enhanced endothelial proliferation, survival, migration, in vitro tube formation, and in vivo Matrigel plug angiogenesis. In a full-thickness skin-wound mouse model, injection of either NCM or HCM significantly accelerated the wound healing. Finally, hASC secretomes were potent in increasing endothelial density and vascular coverage of resident pericytes expressing NG2 and nestin to the lesion site, potentially contributing to blood vessel maturation. Overall, our data suggest that serum-free media or hypoxic preconditioning enhances the vascular regenerative effects of hASC secretome in a preclinical wound healing model.

Emerging Strategies in Mesenchymal Stem Cell-Based Cardiovascular Therapeutics

“…Proliferation assays and colorimetric assessments are also performed to further validate the therapeutic potential of the secretome [127][128][129][130]. The efficacy of the secretome in wound healing is evaluated both in vitro and in vivo [132]. For in vitro studies, tissue defects are treated with varying concentrations of the secretome, and cell migration is assessed using fluorescence analysis [132].…”

“…The efficacy of the secretome in wound healing is evaluated both in vitro and in vivo [132]. For in vitro studies, tissue defects are treated with varying concentrations of the secretome, and cell migration is assessed using fluorescence analysis [132]. In vivo studies involve applying the secretome to damaged skin in animal models, followed by a histological examination post regeneration [132].…”

The Immunomodulatory Role of Cell-Free Approaches in SARS-CoV-2-Induced Cytokine Storm—A Powerful Therapeutic Tool for COVID-19 Patients

“…Until today, numerous studies published positive outcomes of MCS-CM on the improvement of several pathological processes present in acute lung injury (ALI); inflammatory lung disease; skin wounds; periodontitis; neurodegenerative diseases, such as Parkinson's and Alzheimer's disease; or other various immune-mediated inflammatory diseases [62,[74][75][76][77][78][79][80][81][82][83]. For instance, in studies published by Goolaerts et It is well known that the typical pathophysiological features of ALI are lung inflammation, changes in alveolar ion transport, and increased endothelial permeability, often resulting in acute respiratory distress syndrome (ARDS).…”

Effectiveness of Secretome from Human Umbilical Cord Mesenchymal Stem Cells in Gel (10% SM-hUCMSC Gel) for Chronic Wounds (Diabetic and Trophic Ulcer) – Phase 2 Clinical Trial

“…6 diabetic foot ulcers, as well as conditions that stop the skin from healing itself, like aging and skin damage from the environment. [28][29][30] In surgery, the secretome of the human umbilical cord has been looked at to see if it can help heal and grow back damaged tissue. It has been shown to have growth factors and cytokines that can help make new blood vessels and encourage the growth of cells that help mend tissue.…”