Jiang Wen-Hui, Ma Ai-Qun, Zhang Yan-Min, Han Ke, Liu Yu, Zhang Zeng-Tie, Wang Ting-Zhong, Huang Xin, Zheng Xiao-Pu
Cardiovascular Department, the First Hospital of Xi'an Jiaotong University, Ministry of Education, Xi'an 710061, China.
Sheng Li Xue Bao. 2005 Oct 25;57(5):566-72.
The present study aimed to determine the role of tissue injury in migration of mesenchymal stem cells (MSCs) intravenously transplanted into heart and to establish experimental basis for improving stem cell therapy in its targeting and effectiveness. MSCs were isolated from bone marrow of male Sprague-Dawley rats and purified by density centrifuge and adhered to the culture plate in vitro. Female rats were divided randomly into four groups. Myocardial ischemia (MI) transplanted group received MSCs infusion through tail vein 3 h after MI and compared with sham-operated group or normal group with MSCs infusion, or control group received culture medium infusion. MI was created in female rats by ligating the left anterior descending coronary artery. The heart was harvested 1 week and 8 weeks after transplantation. The characteristics of migration of MSCs to heart were detected with expression of sry gene of Y chromosome by using fluorescence in situ hybridization (FISH). Ultrastructural changes of the ischemic myocardium of the recipient rats were observed by transmission electron microscope (TEM). One week or 8 weeks after transplantation, sry positive cells were observed in the cardiac tissue in both of MI transplanted group and sham-operated group, the number of sry positive cells being significantly higher in MI transplanted group (P<0.01). No significant difference was found in the number of sry positive cells between 1 week and 8 weeks after transplantation. No sry positive cells were observed in the hearts of control and normal group. In addition, the ultrastructure of some cells located in the peri-infarct area of MI rats with MSCs transplantation was similar to that of MSCs cultured in vitro. These results indicate that MSCs are capable of migrating towards ischemic myocardium in vivo and the fastigium of migration might appear around 1 week after MI. The tissue injury and its degree play an important role in the migration of MSCs.
本研究旨在确定组织损伤在静脉注射到心脏的间充质干细胞(MSCs)迁移中的作用,并为改善干细胞治疗的靶向性和有效性建立实验基础。从雄性Sprague-Dawley大鼠的骨髓中分离出MSCs,通过密度离心法进行纯化,并在体外使其贴附于培养板。将雌性大鼠随机分为四组。心肌缺血(MI)移植组在MI后3小时通过尾静脉输注MSCs,并与假手术组或输注MSCs的正常组进行比较,对照组则输注培养基。通过结扎左冠状动脉前降支在雌性大鼠中制造MI。在移植后1周和8周收获心脏。使用荧光原位杂交(FISH)通过检测Y染色体的sry基因表达来检测MSCs向心脏迁移的特征。通过透射电子显微镜(TEM)观察受体大鼠缺血心肌的超微结构变化。移植后1周或8周,在MI移植组和假手术组的心脏组织中均观察到sry阳性细胞,MI移植组中sry阳性细胞的数量明显更高(P<0.01)。移植后1周和8周之间,sry阳性细胞的数量没有显著差异。在对照组和正常组的心脏中未观察到sry阳性细胞。此外,移植了MSCs的MI大鼠梗死周边区域的一些细胞的超微结构与体外培养的MSCs相似。这些结果表明,MSCs在体内能够向缺血心肌迁移,迁移高峰期可能出现在MI后1周左右。组织损伤及其程度在MSCs的迁移中起重要作用。