Abstract
Mesenchymal stem cells (MSCs) can improve chronic wound healing; however, recent studies suggest that the therapeutic effect of MSCs is mediated mainly through the growth factors and cytokines secreted by these cells, referred to as the MSC secretome. To overcome difficulties related to the translation of cell therapy into clinical use such as efficacy, safety and cost, we propose a hydrogel loaded with a secretome from the recently established human adipose tissue mesenchymal stem cell line (HATMSC2) as a potential treatment for chronic wounds. Biocompatibility and biological activity of hydrogel-released HATMSC2 supernatant were investigated in vitro by assessing the proliferation and metabolic activity of human fibroblast, endothelial cells and keratinocytes. Hydrogel degradation was measured using hydroxyproline assay while protein released from the hydrogel was assessed by interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) ELISAs. Pro-angiogenic activity of the developed treatment was assessed by tube formation assay while the presence of pro-angiogenic miRNAs in the HATMSC2 supernatant was investigated using real-time RT-PCR. The results demonstrated that the therapeutic effect of the HATMSC2-produced factors is maintained following incorporation into collagen hydrogel as confirmed by increased proliferation of skin-origin cells and improved angiogenic properties of endothelial cells. In addition, HATMSC2 supernatant revealed antimicrobial activity, and which therefore, in combination with the hydrogel has a potential to be used as advanced wound-healing dressing.
Highlights
Non-healing diabetic wounds very often lead to leg amputation because at present no satisfactory treatment exists
The potential cytotoxicity of the designed hydrogel dressing to human fibroblasts (MSU-1.1), endothelial cells (HSkMEC.2) and keratinocytes (HaCaT) was studied by examination of cell metabolic activity cultured in the presence or absence of hydrogel spheres
The results of this study indicate that the developed collagen hydrogel loaded with
Summary
Non-healing diabetic wounds very often lead to leg amputation because at present no satisfactory treatment exists. One of the most promising strategies of the experimental trials in this field is mesenchymal stem cells (MSCs)-based therapy [1]. It is attractive due to the differentiation potential of MSCs, their immunomodulatory properties, and paracrine effects [2]. More recently it has been suggested that the use of MSC secretome may be an approach that is better for the treatment of chronic wounds than cell transplantation [3,4,5]. The MSC secretome is the most important factor responsible for the healing effect of these cells. The application of MSC conditioned medium containing bioactive factors, instead of whole cells, can overcome a number of limitations such as poor survival of transplanted cells, invasiveness, and costs of therapy
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