Yao Yang, Shan Tiantian, Li Xiaoying
Department of Anesthesiology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266011, China.
Research Center of Translational Medicine, Central Hospital Affiliated Shandong First Medical University, Jinan 250013, China.
iScience. 2024 Nov 9;27(12):111354. doi: 10.1016/j.isci.2024.111354. eCollection 2024 Dec 20.
Vascular complications caused by diabetes mellitus contribute a major threat to increased disability and mortality of diabetic patients, which are characterized by damaged endothelial cells and angiogenesis. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have been demonstrated to alleviate endothelial cell damage and improve angiogenesis. However, these investigations overlooked the pivotal role of vasculogenesis. In this study, we utilized blood vessel organoids (BVOs) to investigate the impact of high glucose on vasculogenesis and subsequent angiogenesis. We found that BVOs in the vascular lineage induction stage were more sensitive to high glucose and more susceptible to affect endothelial cell differentiation and function. Moreover, hucMSCs can alleviate the high glucose-induced inhibition of endothelial cell differentiation and dysfunction through MAPK signaling pathway downregulation, with the MAPK activator dimethyl fumarate further illustrating the results. Thereby, we demonstrated that high glucose can lead to abnormal vasculogenesis and impact subsequent angiogenesis, and hucMSCs can alleviate this effect.
糖尿病引起的血管并发症对糖尿病患者残疾率和死亡率的增加构成了重大威胁，其特征是内皮细胞受损和血管生成异常。人脐带间充质干细胞（hucMSCs）已被证明可减轻内皮细胞损伤并改善血管生成。然而，这些研究忽略了血管发生的关键作用。在本研究中，我们利用血管类器官（BVOs）来研究高糖对血管发生及后续血管生成的影响。我们发现，处于血管谱系诱导阶段的BVOs对高糖更为敏感，更容易影响内皮细胞的分化和功能。此外，hucMSCs可通过下调MAPK信号通路来减轻高糖诱导的内皮细胞分化抑制和功能障碍，MAPK激活剂富马酸二甲酯进一步证实了这一结果。由此，我们证明了高糖可导致血管发生异常并影响后续血管生成，而hucMSCs可减轻这种影响。
