Clinical trials of myocardial stem cell therapy traditionally have relied on surgery -- infusing the stem cells directly into the heart or injecting them into the myocardium, the heart muscle -- invasive methods that can result in harmful scar tissue, arrhythmia, calcification or small vessel blockages.
"In our research with a swine model of heart failure," said Lee, "we've found that only 1-to-2 percent of MSCs infused into the myocardium grafted into the heart, and there was no evidence that they differentiated into heart muscle cells. In addition, diseased tissue is not a healthy environment for cell growth.
"For these reasons, and because patients with heart failure are not good surgical risks, it made sense to explore a non-invasive cell delivery approach," said Lee. "An important feature of MSCs is their ability to produce a plethora of tissue healing effects, known as "tropic factors," which can be harnessed for stem cell therapy for heart failure.
Lee noted that the multiple trophic factors produced by MSCs have been shown in the literature to be capable of reducing tissue injury, inhibiting fibrosis, promoting angiogenesis, stimulating recruitment and proliferation of tissue stem cells, and reducing inflammatory oxidative stress, a common cause of cardiovascular disease and heart failure.
"Since skeletal muscle is the most abundant tissue in the body and can withstand repeated injection of large number of stem cells, we thought it would be a good method to deliver MSCs," Lee said. "We hypothesized that MSCs, via secretion of these functionally synergistic trophic factors, would be able to rescue the failing heart even when delivered away from the myocardium.
"This study proves our hypothesis," said Lee. "We've demonstrated that injecting MSCs, or trophic factors released by MSCs, into skeletal muscle improved ventricular function, promoted regeneration of heart tissue, decreased cell death and improved o
|Contact: Lois Baker|
University at Buffalo