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

作　　者：Avinash Sanap Kalpana Joshi Supriya Kheur Ramesh Bhonde 

机构地区：[1]Regenerative Medicine Laboratory,Dr.D.Y.Patil Dental College and Hospital,Dr.D.Y.Patil Vidyapeeth,Pimpri,Pune,India [2]Department of Biotechnology,Sinhgad College of Engineering affiliated to Savitribai Phule Pune University,Pune,India

出　　处：《Chronic Diseases and Translational Medicine》2024年第4期340-349,共10页慢性疾病与转化医学（英文版）

基　　金：Council of Scientific and Industrial Research(CSIR),Government of India。

摘　　要：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-αaugmented 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-αand 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-αinfluenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future.

关 键 词：DIFFERENTIATION mesenchymal stem cells MICROENVIRONMENT SECRETOME type 2 diabetes mellitus 

分 类 号：R587.1[医药卫生—内分泌] R78[医药卫生—内科学]