Sun Shuifen, Wang Linping, Tang Qisheng, Yi Jialian, Yu Xin, Cao Yu, Jiang Lihong, Liu Jie
Regenerative Medicine Research Center, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Cell Therapy Engineering Research Center for Cardiovascular Diseases in Yunnan Province, Kunming, Yunnan, China.
Front Cell Dev Biol. 2024 Oct 16;12:1469541. doi: 10.3389/fcell.2024.1469541. eCollection 2024.
Mesenchymal stem cells (MSCs) are safe and effective in treating myocardial infarction (MI) and have broad application prospects. However, the heterogeneity of MSCs may affect their therapeutic effect on the disease. We recently found that MSCs derived from different segments of the same umbilical cord (UC) showed significant difference in the expression of genes that are related to heart development and injury repair. We therefore hypothesized that those MSCs with high expression of above genes are more effective to treat MI and tested it in this study.
MSCs were isolated from 3 cm-long segments of the maternal, middle and fetal segments of the UC (maternal-MSCs, middle-MSCs and fetal-MSCs, respectively). RNA-seq was used to analyze and compare the transcriptomes. We verified the effects of MSCs on oxygen-glucose deprivation (OGD)-induced cardiomyocyte apoptosis . , a rat MI model was established by ligating the left anterior descending coronary artery, and MSCs were injected into the myocardium surrounding the MI site. The therapeutic effects of MSCs derived from different segments of the UC were evaluated by examining cardiac function, histopathology, cardiomyocyte apoptosis, and angiogenesis.
Compared to fetal-MSCs and middle-MSCs, maternal-MSCs exhibited significantly higher expression of genes that are associated with heart development, such as GATA-binding protein 4 (GATA4), and myocardin (MYOCD). Coculture with maternal-MSCs reduced OGD-induced cardiomyocyte apoptosis. In rats with MI, maternal-MSCs significantly restored cardiac contractile function and reduced the infarct size. Mechanistic experiments revealed that maternal-MSCs exerted cardioprotective effects by decreasing cardiomyocyte apoptosis, and promoting angiogenesis.
Our data demonstrated that maternal segment-derived MSCs were a superior cell source for regenerative repair after MI. Segmental localization of the entire UC when isolating hUCMSCs was necessary to improve the effectiveness of clinical applications.
间充质干细胞（MSCs）在治疗心肌梗死（MI）方面安全有效，具有广阔的应用前景。然而，MSCs的异质性可能会影响其对该疾病的治疗效果。我们最近发现，来自同一脐带（UC）不同节段的MSCs在与心脏发育和损伤修复相关的基因表达上存在显著差异。因此，我们假设那些高表达上述基因的MSCs对治疗MI更有效，并在本研究中进行了验证。
从UC的母体段、中段和胎儿段各3厘米长的节段中分离出MSCs（分别为母体MSCs、中段MSCs和胎儿MSCs）。采用RNA测序分析并比较转录组。我们验证了MSCs对氧糖剥夺（OGD）诱导的心肌细胞凋亡的影响。通过结扎左冠状动脉前降支建立大鼠MI模型，并将MSCs注射到MI部位周围的心肌中。通过检测心脏功能、组织病理学、心肌细胞凋亡和血管生成来评估来自UC不同节段的MSCs的治疗效果。
与胎儿MSCs和中段MSCs相比，母体MSCs表现出与心脏发育相关的基因，如GATA结合蛋白4（GATA4）和心肌素（MYOCD）的显著高表达。与母体MSCs共培养可减少OGD诱导的心肌细胞凋亡。在MI大鼠中，母体MSCs显著恢复了心脏收缩功能并减小了梗死面积。机制实验表明，母体MSCs通过减少心肌细胞凋亡和促进血管生成发挥心脏保护作用。
我们的数据表明，母体段来源的MSCs是MI后再生修复的优质细胞来源。分离人脐带间充质干细胞时对整个UC进行节段定位对于提高临床应用效果是必要的。
