From Primary MSC Culture of Adipose Tissue to Immortalized Cell Line Producing Cytokines for Potential Use in Regenerative Medicine Therapy or Immunotherapy

Int J Mol Sci. 2021 Oct 23;22(21):11439. doi: 10.3390/ijms222111439.

Abstract

For twenty-five years, attempts have been made to use MSCs in the treatment of various diseases due to their regenerative and immunomodulatory properties. However, the results are not satisfactory. Assuming that MSCs can be replaced in some therapies by the active factors they produce, the immortalized MSCs line was established from human adipose tissue (HATMSC1) to produce conditioned media and test its regenerative potential in vitro in terms of possible clinical application. The production of biologically active factors by primary MSCs was lower compared to the HATMSC1 cell line and several factors were produced only by the cell line. It has been shown that an HATMSC1-conditioned medium increases the proliferation of various cell types, augments the adhesion of cells and improves endothelial cell function. It was found that hypoxia during culture resulted in an augmentation in the pro-angiogenic factors production, such as VEGF, IL-8, Angiogenin and MCP-1. The immunomodulatory factors caused an increase in the production of GM-CSF, IL-5, IL-6, MCP-1, RANTES and IL-8. These data suggest that these factors, produced under different culture conditions, could be used for different medical conditions, such as in regenerative medicine, when an increased concentration of pro-angiogenic factors may be beneficial, or in inflammatory diseases with conditioned media with a high concentration of immunomodulatory factors.

Keywords: HATMSC1; adipose tissue origin mesenchymal stem/stromal cells; cytokine production; immortalized cell line.

MeSH terms

  • Adipose Tissue / metabolism
  • Angiogenesis Inducing Agents / metabolism
  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology*
  • Cytokines / metabolism
  • Endothelial Cells / metabolism
  • Humans
  • Immunomodulation
  • Immunotherapy
  • Mesenchymal Stem Cells / metabolism*
  • Neovascularization, Physiologic / physiology
  • Regenerative Medicine / methods
  • Regenerative Medicine / trends

Substances

  • Angiogenesis Inducing Agents
  • Culture Media, Conditioned
  • Cytokines