4.7 Article

HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds-In Vitro Study

Journal

Publisher

MDPI
DOI: 10.3390/ijms222212241

Keywords

adipose tissue-derived mesenchymal stem cells; mesenchymal stem cell secretome; MSC secretome; chronic wound; collagen hydrogel

Funding

  1. Fundation for Polish Science
  2. European Union under the European Regional Development Fund [POIR.04.04.00-00-3024/17-00]
  3. Science Foundation Ireland (SFI)
  4. European Regional Development Fund (ERDF) [13/RC/2073 P2]

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A potential treatment for chronic wounds using a hydrogel loaded with secretome from adipose tissue mesenchymal stem cells has been proposed. The biocompatibility and pro-angiogenic activity of the hydrogel-released factors were investigated, showing positive effects on skin-origin cell proliferation and endothelial cell angiogenic properties. Additionally, antimicrobial activity was observed in the secretome, indicating its potential use as an advanced wound-healing dressing in combination with the hydrogel.
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.

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