Kim Sang-Min, Li Qiang, An Ju-Hyun, Chae Hyung-Kyu, Yang Ji-In, Ryu Min-Ok, Nam Aryung, Song Woo-Jin, Youn Hwa-Young
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
J Vet Med Sci. 2019 Dec 5;81(11):1663-1670. doi: 10.1292/jvms.19-0337. Epub 2019 Oct 2.
The paracrine function of mesenchymal stem cells (MSCs) during transplantation has been recently studied due to its poor differentiation ratio. Dimethyloxalylglycine (DMOG) has been used to promote angiogenesis in experimental animal models, however, comparable approaches for canine MSCs are not sufficient. In the present study, we assessed whether DMOG improves angiogenesis in canine adipose tissue-derived mesenchymal stem cells (cAT-MSCs). cAT-MSCs were treated with DMOG and their effect on angiogenesis was investigated by cell proliferation assay, western blotting, and tube formation assay. Dimethyloxalylglycine preconditioning enhanced the expression of vascular endothelial growth factor (VEGF) among pro-angiogenic factors in cAT-MSCs via hypoxia-inducible factor-1α stabilization. Dimethyloxalylglycine primed-cAT-MSC-conditioned media increased angiogenesis in human umbilical vein endothelial cells. These results suggest that DMOG conditioning of cAT-MSCs augmented the secretion of VEGF, which acted as a prominent pro-angiogenic factor during angiogenesis. DMOG-primed cAT-MSCs may have the potential to induce beneficial effects in ischemic diseases in clinical trials.
由于间充质干细胞（MSCs）移植后的分化率较低，其旁分泌功能近来受到了研究。二甲基乙二酰甘氨酸（DMOG）已被用于在实验动物模型中促进血管生成，然而，针对犬间充质干细胞的类似方法并不充分。在本研究中，我们评估了DMOG是否能改善犬脂肪组织来源的间充质干细胞（cAT-MSCs）的血管生成。用DMOG处理cAT-MSCs，并通过细胞增殖试验、蛋白质印迹法和管腔形成试验研究其对血管生成的影响。二甲基乙二酰甘氨酸预处理通过稳定缺氧诱导因子-1α增强了cAT-MSCs中促血管生成因子血管内皮生长因子（VEGF）的表达。经二甲基乙二酰甘氨酸预处理的cAT-MSC条件培养基增加了人脐静脉内皮细胞的血管生成。这些结果表明，对cAT-MSCs进行DMOG预处理可增强VEGF的分泌，而VEGF在血管生成过程中是一种重要的促血管生成因子。经DMOG预处理的cAT-MSCs可能在临床试验中对缺血性疾病产生有益影响。
