Gong Xuhe, Fan Guangpu, Wang Wei, Wang Guogan
Emergency and Critical Center, Department of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Cell Physiol Biochem. 2014;34(6):2245-55. doi: 10.1159/000369667. Epub 2014 Dec 8.
Mesenchymal stem cell (MSC) transplantation is a promising therapy for cardiac repair. However, the efficacy is limited by the poor viability of MSCs in the infarcted heart. Recent findings have implicated that trimetazidine (TMZ) enhanced the survival of the stem cells under various conditions. However, as the stem cells in these studies were animal-derived, little information is available about the effects of TMZ on human MSCs. Herein, we propose that TMZ may protect human MSCs against apoptosis induced by Hypoxia/Serum deprivation (H/SD).
Human umbilical cord MSCs (UC-MSCs) from Wharton's jelly were pretreated with 10µM TMZ of H/SD with or without the Akt inhibitor LY294002. The morphological changes were assessed using Hoechst 33342. Apoptosis was evaluated via Annexin V/PI staining; and apoptosis-related proteins were detected using Western-blot. Protein chip technology was used to screen for differences between the cell supernatants.
TMZ had a significant protective effect against H/SD-induced apoptosis, accompanied by an increase in Bcl-2 and p-Akt. The TMZ-mediated anti-apoptotic effect on MSCs could be attenuated by treatment with LY294002. Moreover, protein chip assays showed that TMZ treatment increased the paracrine functions of MSCs.
Trimetazidine protects human UC-MSCs from H/SD-induced apoptosis via the Akt pathway and may therefore be a potentially useful therapeutic adjunct for transplanting MSCs into damaged heart after myocardial infarction.
间充质干细胞（MSC）移植是一种很有前景的心脏修复治疗方法。然而，梗死心脏中MSC的低存活率限制了其疗效。最近的研究发现，曲美他嗪（TMZ）在各种条件下可提高干细胞的存活率。然而，由于这些研究中的干细胞是动物来源的，关于TMZ对人MSC影响的信息很少。在此，我们提出TMZ可能保护人MSC免受缺氧/血清剥夺（H/SD）诱导的细胞凋亡。
来自华通胶的人脐带MSC（UC-MSC）在有或没有Akt抑制剂LY294002的情况下，用10µM TMZ预处理H/SD。使用Hoechst 33342评估形态变化。通过Annexin V/PI染色评估细胞凋亡；并使用蛋白质印迹法检测凋亡相关蛋白。使用蛋白质芯片技术筛选细胞上清液之间的差异。
TMZ对H/SD诱导的细胞凋亡具有显著的保护作用，同时Bcl-2和p-Akt增加。LY294002处理可减弱TMZ介导的对MSC的抗凋亡作用。此外，蛋白质芯片分析表明TMZ处理增加了MSC的旁分泌功能。
曲美他嗪通过Akt途径保护人UC-MSC免受H/SD诱导的细胞凋亡，因此可能是心肌梗死后将MSC移植到受损心脏中的一种潜在有用的治疗辅助药物。
