Endothelial and Pericyte Differentiation of Human Mesenchymal Stem Cells Were Inhibited in Diabetic Condition

Background and Aim: Human mesenchymal stem cells (hMSCs) with selfrenewalactivity, trans-differentiation into different lineages contribute to the reconstitution of injured tissues by augmentation of angiogenesis. Itwas reported that in patients with diabetes type 2 DM2 deficient andabnormal angiogenesis are very common. hMSCs are more sensitive tothe persistent diabetic condition. In the present study, we aimed to studythe effect of sera from DM2 patients on the differentiation capacity ofhMSCs into endothelial and pericyte cells.Methods: For in vitro assays, hMSCs were classified into three groups asfollows; Control: cells received FBS; Non-diabetic: cells received serafrom healthy subjects and Diabetic groups treated with diabetic sera.hMSCs were exposed to DMEM/LG containing 10% FBS, healthy anddiabetic sera over a period of 7 days. To measure the differentiationcapacity of hMSCs, cells were incubated with endothelial and pericytesdifferentiation media after 7-day exposure to FBS and sera from healthyand diabetic subjects. To monitor the endothelial- and pericyte-likedifferentiation, the expression of VE-cadherin (CD144) (Cat no 53-1449-41, ebioscience) and NG2 (Cat no: 53-6504-82, ebioscience) weremonitored by a flow cytometry and low-density lipoprotein (LDL) uptakeassays. Data are shown as mean SD. One-way analysis of variance(ANOVA) and Tukey post hoc test was used in experiments betweengroups. Values of P < 0.05 were considered statistically significant.Results: Diabetic serum inhibited hMSCs differentiation capacity bydown-regulating VE-cadherin as compared to cells from FBS and nondiabeticgroups (P diabetic sera vs. FBS <0.000001; P diabetic sera vs.non-diabetic <0.01). The maximum level of VE-cadherin revealed inFBS group which was more than non-diabetic counterpart (P < 0.0001).In the absence of differentiation factors, 14-day incubation of hMSCswith FBS, non-diabetic and diabetic sera showed a similar pattern in thedynamic of VE-cadherin. Data from fluoresce microscopy confirmed thatthe potential of hMSCs in FBS and non-diabetic groups to uptake Dil-Ac-LDL after being exposed to endothelial induction medium. Whilethe ability for uptake of Ac-LDL in differentiated cells and lipoproteinlipase activity was profoundly abolished in diabetic condition. There wasa significant inhibitory effect of diabetic sera on pericyte differentiationcapacity in hMSCs (P diabetic sera vs. FBS <0.001). Compared to FBSgroup, we also found a significant reduction in pericyte differentiationof hMSCs (P < 0.01).Conclusion: Our data revealed that DM2 could potentially decrease bothendothelial and pericyte differentiation of hMSCs.

کلیدواژه ها:

Endothelial ، Pericyte ، Human mesenchymal stem cells ، Diabetic Mellitus