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Updated: Sep 7, 2025
Isolation of Rat Adipose Tissue Mesenchymal Stem Cells for Differentiation into Insulin-producing Cells
Published on: August 29, 2022
Fatty acids of type 2 diabetic serum decrease the stemness properties of human adipose-derived mesenchymal stem cells
Parisa Fayyazpour1,2, Effat Alizadeh3, Vahid Hosseini4
1Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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.
Insights
Diabetic serum free fatty acids (FFAs) negatively impact adipose-derived mesenchymal stem cells (AdMSCs), reducing their stemness and regenerative potential. This finding highlights a potential barrier to using AdMSCs for type 2 diabetes treatment.
Area of Science:
- Biomedical Science
- Regenerative Medicine
- Endocrinology
Background:
- Type 2 diabetes is characterized by dyslipidemia and elevated serum free fatty acids (FFAs), which worsen insulin secretion and disease progression.
- Adipose-derived mesenchymal stem cells (AdMSCs) are crucial in regenerative medicine and show promise for diabetes therapy.
Purpose of the Study:
- To investigate the impact of diabetic serum FFAs on the stemness and regenerative properties of AdMSCs.
- To compare the effects of FFAs from diabetic versus nondiabetic menopausal women's serum on AdMSCs.
Main Methods:
- AdMSCs were exposed to FFAs isolated from diabetic and nondiabetic serum.
- Gas-liquid chromatography analyzed serum FFA composition.
- Real-time PCR assessed stemness markers (CD49e, CD90) and Wnt signaling genes (Axin-2, c-Myc).
- BrdU assay, crystal violet staining, and fluorescence staining measured proliferation, colony formation, and glutathione (GSH) levels.
Main Results:
- Diabetic serum exhibited a higher percentage of oleate compared to nondiabetic serum.
- Diabetic FFAs significantly reduced CD90 and c-Myc expression, proliferation rates, colony formation capacity, and GSH levels in AdMSCs.
- Specific reductions included: CD90 (-51%), c-Myc (-48%), proliferation (-35%), colony formation (-50%), and GSH (-62%).
Conclusions:
- Diabetic serum FFAs impair the stemness characteristics of AdMSCs.
- These negative effects may compromise the regenerative capabilities of AdMSCs, posing a challenge for their therapeutic application in type 2 diabetes.
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