Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium

Abstract

Objective

Cell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart.

Methods

Myocardial infarction was produced in 13 domestic swine. At 4 weeks, animals were randomized to receive transepicardial injections of autologous BMMNCs (approximately 24×10⁶ cells, n=8) or phosphate buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral growth, angiogenesis, and infarct size were assessed by angiography, immunohistochemistry, and histomorphometry.

Results

Regional contractility was assessed by transepicardial echocardiography at baseline and 4 weeks following treatment. Angiography revealed a trend toward increased collateral growth in the BMMNC group. Wall motion score index (myocardial function) was similar in both groups at baseline (1.63±0.16 vs. 1.25±0.25, P=.21) and at 4 weeks (1.83±0.22 vs. 1.63±0.38, P=.62). α-Actin-positive smooth muscle cells (SMCs) and Factor VIII positive endothelial cells were significantly greater in the BMMNC-injected animals (314.8±37.4/0.1 vs. 167.1±11.9/0.1 mm² in controls, P=.02, and 363.3±28.2 cells/0.1 mm² vs. 254.4±28.1 cells/0.1 mm² in controls, P=.03, respectively). The number of blood vessels >50 μm in diameter was significantly increased in the BMMNC group (317.9±54.9 vs. 149.1±6.1, P<.05). The size of the infarct area was smaller in the BMMNC-transplanted group than in the controls (P=.015).

Conclusion

BMMNC transplantation appears to improve angiogenesis and reduce infarct size yet results in no improvement in left ventricular function in a chronically infarcted heart.