Pioglitazone administration combined with bone marrow mesenchymal stem cells transplantation improved the heart function of rats with myocardial infarction

doi:10.3969/j.issn.2095-4344.2015.23.016

Abstract

Abstract:

BACKGROUND: Our previous work has demonstrated that bone marrow mesenchymal stem cells (BMSCs) transplantation can improve the heart function of rats with myocardial infarction. However, the overall efficacy is not satisfactory.
OBJECTIVE: To adopt pioglitazone as a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist combined with BMSCs transplantation therapy, thereby further improving cardiac function of rats with myocardial infarction as well as investigating the relevant mechanisms.
METHODS: Twenty Sprague-Dawley rats with myocardial infarction were induced by the left anterior descending coronary artery ligation. The animals were randomized into two groups: BMSCs and BMSCs+pioglitazone. Two weeks later, all the animals received the injection of BMSCs labeled with PKH26 in PBS into the local infarct zone, and then pioglitazone
(3 mg/kg/d) was given by the oral gavage for 2 weeks in the BMSCs+pioglitazone group after the cell transplantation. After 2 weeks of cell transplantation, cardiac functions were evaluated by echocardiography. The expressions of PPAR-γ, Connexin 43 and molecules in TGF-β1/SMAD signaling pathway were examined in different areas of the left ventricle from each harvested heart using immunofluorescent staining, western blot assay and qRT-PCR.
RESULTS AND CONCLUSION: There were no differences in the baseline parameters of cardiac function between the two groups. At 2 weeks after cell transplantation, the left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole and left ventricular ejection fraction were significantly improved in the BMSCs+ pioglitazone group; the expressions of PPAR-γ and Connexin 43 were distinctly increased in different zones of the left ventricle; the levels of TGF-β1, SMAD2 and SMAD3 were obviously attenuated in the infarct zone and border zone. The above-mentioned findings suggest that pioglitazone, a PPAR-γ agonist, can enhance BMSCs potential in improving the heart function after myocardial infarction, and PPAR-γ may elevate the expression of Connexin 43 via the blockade of the TGF-β1/SMAD signaling pathway in the procedure.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

CLC Number:

R394.2

Wu Quan-hua, Hou Jing-ying, Guo Tian-zhu, Zhong Ting-ting, Long Hui-bao, Xing Yue, Zhou Chang-qing, Zheng Shao-xin, Wang Tong. Pioglitazone administration combined with bone marrow mesenchymal stem cells transplantation improved the heart function of rats with myocardial infarction [J]. Chinese Journal of Tissue Engineering Research, 2015, 19(23): 3698-3704.

Figures/Tables 4

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