Zhang Wei, Liu Xiao-Cheng, Yang Li, Zhu De-Lin, Zhang Ya-Dong, Chen Yue, Zhang Hai-Yan
aTianjin Medical University Cardiovascular Clinical College bDepartment of Surgery, TEDA International Cardiovascular Hospital cAlliancells Institute of Stem Cells and Translational Regenerative Medicine Departments of dUltrasound eNuclear Medicine, TEDA International Cardiovascular Hospital fDepartment of Pathology, TEDA Hospital, Tianjin gPeking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Coron Artery Dis. 2013 Nov;24(7):549-58. doi: 10.1097/MCA.0b013e3283640f00.
To investigate the therapeutic effects of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) on myocardial regeneration and cardiac repair after acute myocardial infarction (AMI).
WJ-MSCs were isolated from human umbilical cord under sterile conditions and were cultured and expanded until passage 5. WJ-MSCs were labeled with CM-Dil before transplantation. The mid-third of the left anterior descending artery was ligated surgically to establish a mini-swine AMI model. The miniswines were divided randomly into three groups (n=6 in each): control group, PBS group, and transplantation group. Six weeks later, evaluation of the changes in myocardial perfusion and function was performed by single-photon emission computed tomography and echocardiography in each group. Then, the animals were euthanized and the tissues in the infarcted area were harvested for histopathological examination.
The changes in myocardial perfusion and function were significantly improved in the transplantation group compared with the control and PBS groups (P<0.001). Immunofluorescence results confirmed that the transplanted WJ-MSCs were still alive and part of them appeared to have differentiated into cardiomyocytes and vascular endothelia 6 weeks after transplantation. In the meantime, it was also observed that resident cardiac stem cells also recruited and differentiated into neonatal cardiomyocytes and vascular endothelia. Masson's trichrome showed more viable myocardium and less fibrous tissue in the transplantation group compared with the other two groups (P<0.001). Vessel density was augmented and cell apoptosis was reduced in the transplantation group compared with the control and PBS groups (P<0.001).
WJ-MSCs transplanted by a direct injection into the infarcted area could survive and differentiate into cardiomyocytes and endothelial cells. They also promoted recruitment and differentiation of cardiac stem cells in a porcine model with AMI. In addition, WJ-MSC transplantation reduced apoptosis and fibrosis, enhanced viable myocardium, and thus improved ventricular remodeling and function.
探讨脐带来源的间充质干细胞（WJ-MSCs）对急性心肌梗死（AMI）后心肌再生和心脏修复的治疗作用。
在无菌条件下从人脐带中分离出WJ-MSCs，并进行培养和传代至第5代。移植前用CM-Dil对WJ-MSCs进行标记。通过手术结扎左前降支动脉中部建立小型猪AMI模型。将小型猪随机分为三组（每组n = 6）：对照组、PBS组和移植组。六周后，通过单光子发射计算机断层扫描和超声心动图对每组心肌灌注和功能变化进行评估。然后对动物实施安乐死，取梗死区域组织进行组织病理学检查。
与对照组和PBS组相比，移植组心肌灌注和功能变化得到显著改善（P < 0.001）。免疫荧光结果证实，移植的WJ-MSCs在移植6周后仍存活，部分细胞似乎已分化为心肌细胞和血管内皮细胞。同时，还观察到心脏内源性干细胞也被募集并分化为新生心肌细胞和血管内皮细胞。与其他两组相比，移植组Masson三色染色显示存活心肌更多，纤维组织更少（P < 0.001）。与对照组和PBS组相比，移植组血管密度增加，细胞凋亡减少（P < 0.001）。
直接注射到梗死区域的WJ-MSCs能够存活并分化为心肌细胞和内皮细胞。它们还促进了AMI猪模型中心脏干细胞的募集和分化。此外，WJ-MSC移植减少了细胞凋亡和纤维化，增强了存活心肌，从而改善了心室重构和功能。
