By Ashley Starkweather, B.S. and Asher Kimchi M.D.

Houston, TX - Stem-cell based therapy is a promising therapy for severe post-infarction systolic left ventricular dysfunction. Among the multipotent cells found in bone marrow are mesenchymal stem cells (MSCs) that are capable of differentiating into vascular endothelial cells. It was found that implantation of MSCs into chronically ischemic myocardium results in differentiation into smooth muscle cells and endothelial cells. This ultimately results in increased vascularity and improved cardiac function. This study was published by Guilherme V. Silva, M.D. et al from the Texas Heart Institute at St. Luke’s Episcopal Hospital in Houston, Texas, in the January 18, 2005 issue of Circulation.

One promising alternative pharmacological treatment for chronic ischemia is stem-cell based therapy. Stem cells are capable of differentiating into cardiomyocytes and cell grafting within damaged tissue. Thus, limiting the consequences of the loss of myocardium and contractile function. The aim of this study was to determine whether bone marrow-derived MSC transplantation would improve the morphology and function of the heart in a chronic canine model of myocardial ischemia.

Initially, canine allogenic MSC was isolated. Then, twelve dogs underwent ameroid constrictor placement, which is a surgical occlusion technique. Thirty days later, 6 dogs received MSC (100X 10⁶ MSCs/10 mL saline) and 6 dogs received 10 mL of saline only. All were euthanized at 60 days. Echocardiography laboratory samples of WBC, C-reactive protein (CRP), CK-MB and troponin were measured. Immunohistopathological analyses were performed.

Mean Left Ventricular Ejection Fraction (LVEF) was similar in both groups at baseline but higher in the treated dogs at 60 days (P=0.004).  WBC and CRP levels were similar in both groups. CK-MB and troponin I increased from baseline to 48 hours and eventually returned to baseline.  Histopathology revealed reduced fibrosis and increased vascularity in the treated group.

The study showed engrafted MSCs present in vessel walls were positive for alpha-smooth muscle actin, which suggests transdifferentiation into smooth muscle cells. The increase in capillary density and differentiation into smooth muscle and endothelial cells may be a contributory factor to the preserved LVEF at rest and during stress, thus indicating an improvement in total cardiac ischemic burden in both states.

In conclusion, the present study suggests that the implantation of MSCs into chronically ischemic myocardium is safe and effective. MSCs differentiate into smooth muscle and endothelial cells, resulting in increased vascularity, and improved cardiac function.

Co-Authors: Silvio Litovsky, MD; Joao A.R. Assad, MD; Andre L.S. Sousa, MD; Bradley J. Martin, PhD; Deborah Vela, MD; Stephanie C. Coulter, MD; Jing Lin, MD; Judy Ober, DVM; William K. Vaughn, PhD; Rodrigo V.C. Branco, MD; Edie M. Oliveira, MD; Rumin He, PhD; Yong-Jian Geng, MD, PhD; James T. Willerson, MD; Emerson C. Perin , MD, PhD