Growth Factors to Heal the Heart

When the heart suffers a heart attack, local areas of the heart experience cell death as a result of blockage in a coronary vessel. The cell death is followed by local inflammation which causes further cell death and produces a heart scar. This produces a situation in which a portion of the heart does not contract and also does not conduct impulses to beat. Can this dead heart tissue live again?

Several experiments have used stem cells to refurbish the dead heart tissue, and a variety of different stem cells can clearly produce new heart cells that help the heart beat better. Can growth factors that stimulate cell growth and division do a similar job?

Just injecting growth factors into the bloodstream will not do because the growth factors will not spend any appreciable time in or around the heart cells. Is there another way to do it? Yes. The answer is hydrogels.

Hydrogels are semi-solid materials that can be made and in which the growth factors can be embedded. The hydrogels are gradually degraded while they release growth factors into the heart tissue. The slow but stead release of various growth factors can induce the heart to heal itself.

Works from the laboratory of Michael E. Davis at Georgia Institute of Technology and Emory University School of Medicine in Atlanta, Georgia have published a paper in PLoS ONE describing this very strategy. Using rats that had suffered heart attacks, Davis and his group applied a polyethylene glycol-based hydrogel laced with two growth factors, hepatic growth factor (HGF) and vascular endothelial growth factor (VEGF) to the hearts of these animals.

There were no immediate effects to the application of these hydrogels as determined by electrocardiograms. However, with the passage of time, some remarkable changes to the hearts of these rats were observed. Three weeks after the application of hydrogels to rat hearts, animals treated hydrogel material only, injected with growth factors only showed no significant improvement over those rats that were not injected with anything. But those rats whose hearts had been injected with hydrogels laced with VEGF showed a 50% increase in blood vessel density and those injected with hydrogel imbued with HGF and VEGF showed a 100% increase in blood vessel density. These same rats also showed a huge reduction in the size of the heart scar (41.5 % vs 13.9% fibrosis), and also showed significant increased in heart function after three weeks.

Why did these growth factors work so well? Several experiments conducted by Davis’ group showed that the stem cell population in the heart, the cardiac progenitor cells or CPCs, were pitched into overdrive by the growth factors, In short, in the presence of these two growth factors, the cells went nuts. They went to area where the hydrogel had been applied and made new heart muscle cells and blood vessels.

Therefore, these two growth factors can be applied to the heart to elicit healing within the heart after a heart attack. The hydrogels keep the growth factors there and release them slowly so tat they can perform their healing magic.

Hopefully this experiment will lead to preclinical studies in larger animals (pigs and sheep), and then, hopefully, clinical trials in human patients.  See Salimath AS, et al., PLoS ONE 2012 7(11) e50980.