Su Jin-Zi, Cai Wen-Qin, Lin Mei-Ping, Lin Mao-Hai, Lin Ming
Departmnent of Cardiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009 Nov;25(4):521-6.
To investigate the effects of hepatocyte growth factor gene transfected MSCs transplantation on cardiac function and fibrosis in rats heart failure model induced by adriamycin.
MSCs were isolated from SD rats by density gradient centrifugation, purified, and transfected with Ad-hHGF. ELISA were used to detect the protein expression of hHGF in these MSCs. Forty SD rats underwent intraperitoneal injection with adriamycin to induce heart failure model. 8 healthy rats served as control, 24 survival rats were randomly divided into 3 groups (n = 8): Rats in Ad-hHGF transfected MSCs group were injected with Ad-hHGF transfected MSCs 2 weeks after the establishment of the model, rats in MSC group injected with suspension of MSCs only, and model group was injected with cold culture fluid. Heart function was evaluated by a physiological recorder 4 weeks after cell transplantation. Myocardial cell morphology and interstitial collagen were studied by electron microscope and were stained by Sirus red. TGF-beta1 was detected by immunohistochemical method.
(1) MSCs could be transfected efficiently by Ad-hHGF, manifested by a higher level of expression in vitro, persisting 14 days at least. (2) Four weeks after the cells transplantion, cardiac necrosis in MSC-hHGF rats was improved when compared with those in the MSCs (P < 0.05) and Model group (P < 0.01). The heart function of the MSC-hHGF rats was greatly improved with an significant increase in LVSP and + dp/dt(max), although LVEDP still highter than that of normal rats. (3) MSC-Ad-hHGF decreased Myocardial collagen content and the level of TGFbeta1 compaired with MSCs transplanted rats (P < 0.01).
Transplantation of HGF gene transfected MSCs improved heart function, decreased myocardial collagen and the level of TGFbeta1.
探讨肝细胞生长因子基因转染的间充质干细胞移植对阿霉素诱导的大鼠心力衰竭模型心功能及纤维化的影响。
采用密度梯度离心法从SD大鼠分离间充质干细胞，纯化后用Ad-hHGF转染。用ELISA检测这些间充质干细胞中hHGF的蛋白表达。40只SD大鼠腹腔注射阿霉素诱导心力衰竭模型。8只健康大鼠作为对照，24只存活大鼠随机分为3组（n = 8）：Ad-hHGF转染间充质干细胞组在模型建立后2周注射Ad-hHGF转染的间充质干细胞，间充质干细胞组仅注射间充质干细胞悬液，模型组注射冷培养液。细胞移植4周后用生理记录仪评估心功能。通过电子显微镜研究心肌细胞形态和间质胶原，并用天狼星红染色。用免疫组织化学方法检测TGF-β1。
（1）Ad-hHGF能有效转染间充质干细胞，体外表达水平较高，至少持续14天。（2）细胞移植4周后，与间充质干细胞组（P < 0.05）和模型组（P < 0.01）相比，MSC-hHGF大鼠的心肌坏死得到改善。MSC-hHGF大鼠的心功能显著改善，LVSP和 + dp/dt(max)显著增加，尽管LVEDP仍高于正常大鼠。（3）与移植间充质干细胞的大鼠相比，MSC-Ad-hHGF降低了心肌胶原含量和TGFβ1水平（P < 0.01）。
HGF基因转染的间充质干细胞移植改善了心功能，降低了心肌胶原含量和TGFβ1水平。
