The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing

Int J Mol Sci. 2017 Jul 25;18(8):1614. doi: 10.3390/ijms18081614.

Abstract

Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan and Prisma® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that mesoglycan and Prisma® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses.

Keywords: Prisma® Skin; angiogenesis; glycosaminoglycans; mesoglycan; skin wound healing.

MeSH terms

  • Cell Movement
  • Cell Survival / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Glycosaminoglycans / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hyaluronan Receptors / metabolism
  • In Vitro Techniques
  • Neovascularization, Physiologic / drug effects*
  • Pharmaceutical Preparations
  • Skin / blood supply*
  • Wound Healing / drug effects*

Substances

  • CD44 protein, human
  • Glycosaminoglycans
  • Hyaluronan Receptors
  • Pharmaceutical Preparations
  • mesoglycan