Objective To investigate if the L-carnitine can improve the survival rate of transplanted MSCs after myocardial infarction, and enhance therapeutic effect of MSCs.
Methods Five rats were separately obtained, MSCs were isolated and purified by density-gradient centrifugation and adherence method. 60 rats were randomly assigned into five groups: sham operation group (n=12), model group (n=12), LC group (n=12), MSCs group (n=12), and LC+MSCs group (n=12). Rats in the sham operation group received chest open, without ligation of the left coronary artery. In other four groups, the left coronary artery was ligated to establish myocardial infarction models. Following 20 min of coronary artery ligation, 250 μl MSCs (2×106 cells per animal) were injected into the left ventricular wall of the infarcted hearts (50 μl into1 injected foci) and peri-infarct zone (200 μl into 4 injected foci) in MSC group and LC+MSCs group, rats in the model group and sham operation group received intramyocardial injection of the same volume of cell-free DMEM. From 3 days prior to MSC transplantation to ended 4 days post-transplantation, rats in the LC group and LC+MSCs were separately administrated with LC (100 mg/(kg·d))intraperitoneally. Rats in the model group, sham operation group and MSCs group separately administrated with PBS (100 mg/ (kg·d)). The heart function was evaluated by left ventricular ejection fraction, shortening fraction, and the indexes of blood dynamics 4 weeks after transplantation, the survival of MSCs and myocardial fibrosis in myocardial infarction were detected using immunohistochemistry.
Results Compared with the model group, ejection fraction, fractional shortening, the left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), the maximal rate of isovolumetric contraction (+dp/dtmax, −dp/dtmax) and myocardial fibrosis were improved in the group MSCs, group LC and group LC+MSCs (p<0.05); Compared with the MSCs group, the survival of MSCs, ejection fraction, fractional shortening, LVESP, LVEDP, +dp/dtmax, −dp/dtmax and myocardial fibrosis in group LC+MSCs have significantly improved (p<0.05).
Conclusion Cardiac function and myocardial fibrosis can be improved by LC and MSCs in acute myocardial infarction rat models, but the effect is limited. Pretreated with LC, MSCs transplantation will achieve better result for improving the survival of MSCs.
- Acute myocardial infarction
- bone marrow mesenchymal stem cells
- cell transplantation
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