Direct injection of autologous mesenchymal stromal cells improves myocardial function

Abstract

Cell-based therapies have been employed with conflicting results. Whether direct injection of ex-vivo expanded autologous marrow stromal cells (MSCs) would improve the function of ischemic myocardium and enhance angiogenesis is not well defined. In a porcine model of chronic ischemia, MSCs were isolated and cultured for 4 weeks. Sixteen animals were random divided into two groups to receive either direct intramyocardial injection of autologous MSCs, or equal volumes and injections sites of saline. Cine MRI and epicardial echocardiography were performed just prior to the injections and again 6 weeks later at the time of sacrifice at which point tissue was also analyzed. Myocardial function as assessed by regional wall thickening (as measured by dobutamine stress echocardiograms) demonstrated a 40.9% improvement after cell treatment of the ischemic zone (p = 0.016) whereas the saline treated animals only had a 3.7% change (p = 0.82) compared to baseline. The left ventricular ejection fractions of MSC group showed 19.5% improvement from baseline 35.9 ± 3.8% to 42.9 ± 5.8% (p = 0.049). Increased vascularity was found in the MSC group compared to controls (0.80 ± 0.30 vs 0.50 ± 0.19 capillary/myocyte ratio, p = 0.018). Direct injection of autologous MSCs promotes angiogenesis and enhances the functional improvements following chronic myocardial ischemia. This suggests that the angiogenesis engendered by cell treatment may be physiologically meaningful by improving the contractility of ischemic myocardium.

Mesenchymal stem cells or cardiac progenitors for cardiac repair? A comparative study

“…Most of the positive myocardial differentiation data involving MSCs have been obtained after transplantation of these cells in rats or mice [34,41]. However, when MSCs were transplanted in the chronic infarction swine model, these cells differentiated into vascular smooth muscle cells or endothelial cells but, in accordance with the results presented here, not into cardiomyocytes [42].…”

Ultrasound-guided Transthoracic Intramyocardial Injection in Mice

“…Recent cell based therapy trials in myocardial infarction models have described an open thoracotomy approach to the delivery of injectate [12][13][14] . An important factor in the success of a myocardial therapeutic intervention hinges on the choice of delivery route.…”

Neo-Revascularization as the Potential Treatment for Patient Suffering from Pulmonary Arterial Hypertension (Myth or Reality)

“…Many investigators now believe that in adults, bone marrow-derived stem cells can be recruited to and incorporated into tissues undergoing neovascularisation [7][8][9][10][11]. Therefore, stem cells have been used as an alternative therapeutic strategy for ischemic cardiovascular diseases that cannot be treated by routine interventional approaches [12][13][14][15].…”