January 18, 2005
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
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.
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