Guo Xueyan, Wang Junyan, Su Rong, Luo Dan, Zhao Keli, Li Yan
Department of Laboratory Medicine, Foshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Foshan, 528000, China.
Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Clin Proteomics. 2024 Dec 30;21(1):69. doi: 10.1186/s12014-024-09521-5.
The therapeutic potential of mesenchymal stem cells (MSCs) may be partly attributed to their secretion growth factors, cytokines and chemokines. In various preclinical studies, the use of MSC-conditioned media (CM) has demonstrated promising potential for promoting vascular repair.
To gain a comprehensive understanding of the variations in conditioned media derived from different sources of mesenchymal stem cells (MSCs) including umbilical cord, adipose and bone marrow, we investigated their reparative effects on human umbilical vein endothelial cells (HUVECs) subjected to damage induced by high glucose. Initially, the secreted proteins from the three types of MSCs were assessed using the bicinchoninic acid (BCA) method. Subsequently, we examined the influence of different type of MSC secreted proteins on the proliferation of HUVECs under high glucose conditions. Following this, transwell migration experiments were conducted to evaluate the impact of MSC source on the migration of HUVECs damaged by high glucose. We further compared the effects of adding secreted proteins from the three types of MSCs on the tube formation ability of HUVECs subjected to high glucose damage. Finally, tandem mass tag (TMT) labeling quantitative proteomics was performed to analyze differently expressed proteins in the secreted proteins of three type MSC by using LC-MS/MS.
In this study, we observed a significantly higher secretion of proteins from umbilical cord mesenchymal stem cells (UMSCs) compared to adipose-derived stem cells (ADSCs). Subsequently, we found that the of proliferation HUVECs was significantly improved with supplementing the three MSCs secreted proteins under high glucose medium. Notably, the reparative effects of bone marrow mesenchymal stem cells (BMSCs) and UMSCs were superior to those of ADSCs. Afterwards, UMSCs exhibited the strongest ability to repair cell migration when HUVECs damaged by high glucose. Moreover, all three MSCs' secreted proteins exhibited the ability to enhance tube formation. Importantly, the UMSCs' secretome showed the most pronounced improvement in tube formation, as evidenced by the evaluation of parameters such as the number of nodes, the number of branches, and total length. These findings suggest that the UMSCs' secretome plays a crucial role in biological processes such as vasculature development, cell adhesion, and tissue remodeling. Additionally, the BMSCs' secretome was found to promote vascular development. The results collectively indicate the diverse therapeutic potential of MSC secretomes in influencing various aspects of cellular function and tissue repair.
In conclusion, this study offers a valuable reference for the selection of more suitable sources of mesenchymal stem cells (MSCs) in the treatment of diabetic cardiovascular disease.
间充质干细胞(MSCs)的治疗潜力可能部分归因于其分泌的生长因子、细胞因子和趋化因子。在各种临床前研究中,使用MSC条件培养基(CM)已显示出促进血管修复的潜在前景。
为全面了解来自不同来源间充质干细胞(包括脐带、脂肪和骨髓)的条件培养基的差异,我们研究了它们对高糖诱导损伤的人脐静脉内皮细胞(HUVECs)的修复作用。首先,使用二辛可宁酸(BCA)法评估三种类型MSCs分泌的蛋白质。随后,我们检测了不同类型MSC分泌蛋白在高糖条件下对HUVECs增殖的影响。在此之后,进行Transwell迁移实验以评估MSC来源对高糖损伤的HUVECs迁移的影响。我们进一步比较了添加三种类型MSCs分泌蛋白对高糖损伤的HUVECs管形成能力的影响。最后,采用串联质谱标签(TMT)标记定量蛋白质组学,通过液相色谱-串联质谱(LC-MS/MS)分析三种类型MSC分泌蛋白中的差异表达蛋白。
在本研究中,我们观察到脐带间充质干细胞(UMSCs)分泌的蛋白质明显高于脂肪来源干细胞(ADSCs)。随后,我们发现补充三种MSCs分泌蛋白后,高糖培养基中HUVECs的增殖显著改善。值得注意的是,骨髓间充质干细胞(BMSCs)和UMSCs的修复作用优于ADSCs。之后,当HUVECs受到高糖损伤时,UMSCs表现出最强的修复细胞迁移能力。此外,所有三种MSCs的分泌蛋白均表现出增强管形成的能力。重要的是,通过对节点数、分支数和总长度等参数的评估,UMSCs的分泌组在管形成方面表现出最显著的改善。这些发现表明,UMSCs的分泌组在血管发育、细胞粘附和组织重塑等生物学过程中起关键作用。此外,发现BMSCs的分泌组可促进血管发育。结果共同表明MSC分泌组在影响细胞功能和组织修复的各个方面具有不同的治疗潜力。
总之,本研究为糖尿病心血管疾病治疗中选择更合适的间充质干细胞(MSCs)来源提供了有价值的参考。