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

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). 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). 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. 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. Adipose tissue‐derived mesenchymal stem cells secretome from healthy individuals restore the tumor necrosis factor‐α influenced differentiation fate of dDPMSCs and therefore can be explored for type 2 diabetes mellitus clinical management in the future. Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals are known to exhibit increased adipogenesis and decreased osteogenesis.Adipose tissue‐derived MSCs (ADMSCs) secretome from healthy individuals modulate the TNF‐α influenced differentiation fate of MSCs obtained from diabetic individuals into adipocytes and osteocytes.ADMSCs secretome can be explored in restoring the disturbed microenvironment of MSCs and offering an effective alternative for the T2DM in future. Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals are known to exhibit increased adipogenesis and decreased osteogenesis. Adipose tissue‐derived MSCs (ADMSCs) secretome from healthy individuals modulate the TNF‐α influenced differentiation fate of MSCs obtained from diabetic individuals into adipocytes and osteocytes. ADMSCs secretome can be explored in restoring the disturbed microenvironment of MSCs and offering an effective alternative for the T2DM in future.