Fatty acids of type 2 diabetic serum decrease the stemness properties of human adipose-derived mesenchymal stem cells

J Cell Biochem. 2022 Jul;123(7):1157-1170. doi: 10.1002/jcb.30270. Epub 2022 Jun 20.

Abstract

In type 2 diabetes, dyslipidemia and increased serum free fatty acids (FFAs) exacerbate the development of the disease through a negative effect on insulin secretion. Adipose-derived mesenchymal stem cells (AdMSCs) play a key role in regenerative medicine, and these cells can potentially be applied as novel therapeutic resources in the treatment of diabetes. In this study, AdMSCs were treated with diabetic or nondiabetic serum FFAs isolated from women of menopausal age. Serum FFAs were analyzed using gas-liquid chromatography. The expression level of the stemness markers CD49e and CD90 and the Wnt signaling target genes Axin-2 and c-Myc were evaluated using real-time PCR. The proliferation rate and colony formation were also assessed using a BrdU assay and crystal violet staining, respectively. The level of glutathione was assessed using cell fluorescence staining. Compared to nondiabetic serum, diabetic serum contained a higher percentage of oleate (1.5-fold, p < 0.01). In comparison with nondiabetic FFAs, diabetic FFAs demonstrated decreasing effects on the expression of CD90 (-51%, p < 0.001) and c-Myc (-48%, p < 0.05), and proliferation rate (-35%, p < 0.001), colony formation capacity (-50%, p < 0.01), and GSH levels (-62%, p < 0.05). The negative effect of the FFAs of diabetic serum on the stemness characteristics may impair the regenerative capabilities of AdMSCs.

Keywords: diabetes mellitus; free fatty acids; gas-liquid chromatography; mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Diabetes Mellitus, Type 2* / metabolism
  • Fatty Acids / metabolism
  • Fatty Acids, Nonesterified / metabolism
  • Female
  • Humans
  • Insulin Secretion
  • Mesenchymal Stem Cells* / metabolism

Substances

  • Fatty Acids
  • Fatty Acids, Nonesterified