Chronic Diseases and Translational Medicine (Dec 2024)

Stem cell secretome restore the adipo‐osteo differentiation imbalance in diabetic dental pulp‐derived mesenchymal stem cells

  • Avinash Sanap,
  • Kalpana Joshi,
  • Supriya Kheur,
  • Ramesh Bhonde

DOI
https://doi.org/10.1002/cdt3.125
Journal volume & issue
Vol. 10, no. 4
pp. 340 – 349

Abstract

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Abstract Background Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals exhibit increased adipogenesis and decreased osteogenesis. We investigated the potential of adipose tissue‐derived MSCs (ADMSCs) secretome obtained from healthy individuals in restoring the tumor necrosis factor‐α (TNF‐α) mediated imbalance in the adipo/osteogenic differentiation in the dental pulp‐derived MSCs obtained from T2DM individuals (dDPMSCs). Methods dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of (a) induction cocktail, (b) induction cocktail + TNF‐α, and (c) induction cocktail+ TNF‐α + ADMSCs‐secretome (50%) for 15 and 21 days resp. Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software. Molecular expression of the key genes involved was analyzed by using reverse‐transcription polymerase chain reaction (RT‐PCR). Results Treatment of TNF‐α augmented the adipogenesis (9571 ± 765 vs. 19,815 ± 1585 pixel, p < 0.01) and decreased the osteogenesis (15,603 ± 1248 vs. 11,894 ± 951 pixel, p < 0.05) of dDPMSCs as evidenced by the oil red O and alizarin red staining respectively. Interestingly, dDPMSCs differentiated along with TNF‐α and 50% ADMSCs secretome exhibited enhanced osteogenesis (11,894 ± 951 vs. 41,808 ± 3344 pixel, p < 0.01) and decreased adipogenesis (19,815 ± 1585 vs. 4480 ± 358 pixel, p < 0.01). Additionally, dDPMSCs differentiated along with ADMSCs secretome exhibited decreased expression of PPARg (p < 0.01), C/EBPa (p < 0.05), and FAS (p < 0.01) whereas mRNA expression of Runx2 (p < 0.05), Osterix (p < 0.01), and OCN (p < 0.05) was upregulated as revealed by the RT‐PCR analysis. Conclusion ADMSCs secretome from healthy individuals restore the TNF‐α influenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future.

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