Effects of mesenchymal stem cell transplantatiOn on cardiac function and structure and eIectrophysiology in rabbits with dilated cardiomyopathy
- VernacularTitle:同种异体骨髓间充质干细胞移植对扩张型心肌病模型兔心功能与结构及电生理的影响
- Author:
Gengsheng YU
;
Xing SHEN
;
Jie TIAN
;
Yonghong BAI
;
Jing ZHU
;
Guanxin LIU
;
Yuan CHEN
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2008;12(34):6776-6780
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: The study of cell transplantation to repair injured cardiac muscle and improve cardiac function of dilated cardiomyopathy (DCM) has become a hotspot in recent years. However, the effect of cardiac electrophysiology following transplantation is still unknown.OBJECTIVE: To explore the influence of ailogenic implanted mesenchymal stem cells (MSCs) on cardiac function, structure and electrophysiology of rabbits with DCM.DESIGN, TIME AND SETTING: Randomized controlled animal trial was performed at Electrophysiology Laboratory of Institute of Pediatrics, Chongqing Medical University between January 2004 and May 2006.MATERIALS: Forty-three New Zealand whiterabbits, weighing 3.0-3.5 kg, irrespective of gender, were selected. Adriamycin was produced by Haizheng Medical Products Company of Zhejiang Province, China, No. 050307. The Ultrasonograph SSD-5000 came from Aloka, Japan, and RM6240 multiplying channel electrophysiolograph of Chengdu Instrument Company was applied.METHODS: All animals were randomized into normal group (n=12), cell transplantation group (n=13), and DCM model group (n=13). Except the normal group, adriamycin was applied to create rabbit DCM model, I mg/kg, twice a week for successive 8 weeks. Bone marrow solution was harvested from the remaining 5 rabbits, and MSCs were isolated, amplified and purified using attachment method. Three weeks after modeling, the MSCs were transplanted into left ventricle anterior wall at four sites in cell transplantation group, model group was injected with matching DMEM/FI2 medium, while the normal group was not given any treatment.MAIN OUTCOME MEASURES: At four weeks postoperatively, left ventricular end-diastolic dimension, end systolic dimension,left ventricular ejection fraction, and shortening fraction were monitored by ultrasonograph; the value for monophasic action potential amplitude (MAPA) and the maximum velocity in 0 phase (V,,~), the value for 50% monophasic action potential durations (MAPDs0) and 90% monophasic action potential durations (MAPDg0) were detected by electrophysiolograph. In addition, the cardiac tissues harvested from implanted region were observed by light microscope and electron microscope, and also the expression of cardiac troponin T (cTnT) and connexin 43 (Cx43) was detected through immunohistochemistry.RESULTS: Of 43 rabbits, 9 rabbits each of the transplantation group died of the acute or chronic toxic effects of Adriamycin, finally, 25 rabbits were included in final analysis. Compared with model group, the end systolic dimension was diminished, and the left ventricular ejection fraction and shortening fraction in cell transplantation group were significantly increased (P ＜ 0.05). The MAPDs0 and MAPDgo in cell transplantation group prolonged significantly compared with model group (P ＜ 0.05). In model group,cardiac myocytes appeared mitochondria swelling and hyperplasia, and their sarcomere had different lengths, arranged unevenly,accompanied by abnormal contraction bands. In addition, myolysis was found in parts of myocardium under electron microscope.However, the structural abnormalities in the cell implantation group were less than the DCM model group, and the implanted MSCs could express cTnT and Cx43.CONCLUSION: Allogenic MSCs transplantation can improve cardiac function, lessen structural abnormalities and may inhibit the progression of electrophysiology derangement.
