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Immediate Intramyocardial Bone Marrow-Derived Mononuclear Cells Implantation in Minipig Myocardium After Permanent Coronary Artery Ligation: Magnetic Resonance Imaging With Histopathologic and Immunochemical Correlation

Objectives:To investigate the effects of immediate intramyocardial implantation of autologous bone marrow-derived mononuclear cells (BMDMNCs) in minipig myocardium after coronary artery ligation with magnetic resonance imaging (MRI), histopathologic, and immunochemical studies. Materials and Methods:Of the 12 minipigs subjected to permanent left anterior descending coronary artery ligation, 6 were immediately treated with intramyocardial BMDMNCs (3 × 107 cells) implantation in the infarct area, whereas the other 6 were treated with intramyocardial injection of an equal amount of saline served as controls. Cardiovascular MRIs, including cine, first-pass, and late gadolinium enhancement (LGE) sequences, were performed on postoperative days 3 and 90. Postmortem infarct size and the degree of fibrosis on histopathologic examination were compared between 2 groups. The degree of BMDMNC differentiation was assessed with flow cytometry, whereas engraftment of BMDMNCs and vascular density was evaluated with confocal immunofluorescence microscopy and immunohistochemical staining, respectively. Results:There were no significant differences in cardiac function, first-pass dynamics, and LGE between the BMDMNC-treated group and the control group on day 3. On day 90, the BMDMNC-treated group had significantly higher left ventricular (LV) mass/body-weight ratio, lower end-diastolic or end-systolic LV volume/body-weight ratios, higher ejection fraction, better contractility, greater upslope and peak enhancement of the infarct areas, smaller hypoperfused area on first-pass study, and smaller enhanced area and infarct transmurality on LGE MRI than the control group. Flow cytometry revealed high cellular positivity of mesenchymal stem cell surface markers (CD90 and CD271) of the in vitro expanded cells on day 21 after cell culture. In the infarct and peri-infarct areas of the BMDMNC-treated group, there was limited myogenic-like cell differentiation, some engrafted undifferentiated cells, but prominent CD31-positive endothelial cells. On the other hand, a significantly higher number of &agr;-smooth muscle actin-positive small vessel (≤25 &mgr;m) was noted in the BMDMNC-treated group compared with that in the controls. Conclusions:After myocardial infarction in a swine model, immediate intramyocardial BMDMNCs implantation may promote neovascularization with resultant improvement in LV function, perfusion, and myocardial viability as demonstrated on cardiovascular MRI.