Characterisation of Novel Angiogenic and Potent Anti-Inflammatory Effects of Micro-Fragmented Adipose Tissue

Int J Mol Sci. 2021 Mar 23;22(6):3271. doi: 10.3390/ijms22063271.

Abstract

Adipose tissue and more specifically micro-fragmented adipose tissue (MFAT) obtained from liposuction has recently been shown to possess interesting medicinal properties whereby its application supports pain reduction and may enhance tissue regeneration particularly in osteoarthritis. Here we have characterised samples of MFAT produced using the Lipogems® International Spa system from eight volunteer individuals in order to understand the critical biological mechanisms through which they act. A variation was found in the MFAT cluster size between individual samples and this translated into a similar variation in the ability of purified mesenchymal stem cells (MSCs) to form colony-forming units. Almost all of the isolated cells were CD105/CD90/CD45+ indicating stemness. An analysis of the secretions of cytokines from MFAT samples in a culture using targeted arrays and an enzyme-linked immunosorbent assay (ELISA) showed a long-term specific and significant expression of proteins associated with anti-inflammation (e.g., interleukin-1 receptor alpha (Il-1Rα) antagonist), pro-regeneration (e.g., hepatocyte growth factor), anti-scarring and pro-angiogenesis (e.g., transforming growth factor beta 1 and 2 (TGFβ1/2) and anti-bacterial (e.g., chemokine C-X-C motif ligand-9 (CXCL-9). Angiogenesis and angiogenic signalling were notably increased in primary bovine aortic endothelial cells (BAEC) to a different extent in each individual sample of the conditioned medium whilst a direct capacity of the conditioned medium to block inflammation induced by lipopolysaccharides was shown. This work characterises the biological mechanisms through which a strong, long-lasting, and potentially beneficial effect can be observed regarding pain reduction, protection and regeneration in osteoarthritic joints treated with MFAT.

Keywords: angiogenesis; inflammation; mesenchymal stem cells; micro-fragmented adipose tissue; tissue regeneration.

MeSH terms

  • Adipose Tissue / chemistry*
  • Angiogenesis Inducing Agents / chemistry*
  • Angiogenesis Inducing Agents / isolation & purification
  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Cattle
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology
  • Cytokines / biosynthesis
  • Endothelial Cells
  • Immunophenotyping
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Signal Transduction / drug effects

Substances

  • Angiogenesis Inducing Agents
  • Anti-Inflammatory Agents
  • Culture Media, Conditioned
  • Cytokines