将人骨髓间充质干细胞移植到受损的兔心脏中以改善心脏功能。
Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function.
作者信息
Wang Jian-an, Fan You-qi, Li Chang-ling, He Hong, Sun Yong, Lv Bin-jian
机构信息
Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
出版信息
J Zhejiang Univ Sci B. 2005 Apr;6(4):242-8. doi: 10.1631/jzus.2005.B0242.
OBJECTIVE
The present study was designed to test whether transplantation of human bone marrow-derived mesenchymal stem cells (hMSCs) in New Zealand rabbits with myocardial infarction can improve heart function; and whether engrafted donor cells can survive and transdifferentiated into cardiomyocytes.
METHODS
Twenty milliliters bone marrow was obtained from healthy men by bone biopsy. A gradient centrifugation method was used to separate bone marrow cells (BMCs) and red blood cells. BMCs were incubated for 48 h and then washed with phosphate-buffered saline (PBS). The culture medium was changed twice a week for 28 d. Finally, hematopoietic cells were washed away to leave only MSCs. Human MSCs (hMSCs) were premarked by BrdU 72 h before the transplantation. Thirty-four New Zealand rabbits were randomly divided into myocardial infarction (MI) control group and cell treated group, which received hMSCs (MI+MSCs) through intramyocardial injection, while the control group received the same volume of PBS. Myocardial infarction was induced by ligation of the left coronary artery. Cell treated rabbits were treated with 5 x 10(6) MSCs transplanted into the infarcted region after ligation of the coronary artery for 1 h, and the control group received the same volume of PBS. Cyclosporin A (oral solution; 10 mg/kg) was provided alone, 24 h before surgery and once a day after MI for 4 weeks. Echocardiography was measured in each group before the surgery and 4 weeks after the surgery to test heart function change. The hearts were harvested for HE staining and immunohistochemical studies after MI and cell transplantation for 4 weeks.
RESULTS
Our data showed that cardiac function was significantly improved by hMSC transplantation in rabbit infarcted hearts 4 weeks after MI (ejection fraction: 0.695+/-0.038 in the cell treated group (n=12) versus 0.554+/-0.065 in the control group (n=13) (P<0.05). Surviving hMSCs were identified by BrdU positive spots in infarcted region and transdifferentiated into cardiomyocytes characterized with a positive cardiac phenotype: troponin I.
CONCLUSION
Transplantation of hMSCs could transdifferentiate into cardiomyocytes and regenerate vascular structures, contributing to functional improvement.
目的
本研究旨在检测将人骨髓间充质干细胞（hMSCs）移植到心肌梗死的新西兰兔体内是否能改善心脏功能；以及移植的供体细胞能否存活并转分化为心肌细胞。
方法
通过骨髓穿刺从健康男性获取20毫升骨髓。采用梯度离心法分离骨髓细胞（BMCs）和红细胞。将BMCs孵育48小时，然后用磷酸盐缓冲盐水（PBS）洗涤。每周更换两次培养基，共28天。最后，洗去造血细胞，仅留下间充质干细胞。在移植前72小时用BrdU对人间充质干细胞（hMSCs）进行预标记。34只新西兰兔随机分为心肌梗死（MI）对照组和细胞治疗组，细胞治疗组通过心肌内注射接受hMSCs（MI + MSCs），而对照组接受相同体积的PBS。通过结扎左冠状动脉诱导心肌梗死。在冠状动脉结扎1小时后，将5×10(6)个MSCs移植到梗死区域对细胞治疗组的兔子进行治疗，对照组接受相同体积的PBS。在手术前24小时单独给予环孢素A（口服液；10毫克/千克），心肌梗死后每天一次，持续4周。在每组手术前和手术后4周进行超声心动图测量以检测心脏功能变化。在心肌梗死和细胞移植4周后取出心脏进行HE染色和免疫组织化学研究。
结果
我们的数据显示，心肌梗死后4周，hMSC移植可使兔梗死心脏的心脏功能显著改善（射血分数：细胞治疗组（n = 12）为0.695±0.038，对照组（n = 13）为0.554±0.065（P < 0.05））。通过梗死区域BrdU阳性斑点鉴定出存活的hMSCs，并转分化为具有阳性心脏表型的心肌细胞：肌钙蛋白I。
结论
hMSCs移植可转分化为心肌细胞并再生血管结构，有助于功能改善。
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