HEALTH: Heart attack regeneration therapy closer to human testing


Cardiac regeneration after a heart attack is improved with a combination of a drug to grow blood vessels and self-assembling "nanofibers," according to an animal research study published Wednesday in the journal Science Translational Medicine .

In rats, the therapy improved the growth of blood vessels and boosted heart performance 28 days after heart attacks. A follow-up study in pigs produced results consistent with the rat study. The study's first author was Yi-Dong Lin of Academia Sinica in Taiwan.

The study shows the therapy may be ready in the near future for testing in people, according to a companion article in the journal by a UC San Diego researcher who is developing a similar approach.

Heart attack is the leading cause of death in the United States and the Western world in general. In 2009, nearly 600,000 people died of heart attacks in the U.S., according to the federal Centers for Disease Control and Prevention in Atlanta.

Karen L Christman , a researcher at UCSD's Jacobs School of Engineering, has developed an injectable gel that provides a molecular scaffold that encourages regenerating heart cells to grow where they're needed. Christman has co-founded San Diego-based Ventrix Inc ., which she said intends to begin human testing of its heart attack therapy early next year.

Christman said in a Tuesday interview that the Lin team's approach is promising, because they demonstrated results not only in rats but pigs. Large animals provide indications of effectiveness for human heart treatments that can't be gleaned from small animals, Christman said.

"Overall, this technology has exciting potential, with positive results in both small and large animals," Christman wrote in her review article. "With the addition of a few follow-up studies, this technology has potential for near-future translation into people."

Spurring on nature

Both the Lin and Christman approaches tap into the heart's natural regenerative power. The heart contains various cells that potentially can regrow the heart muscle cells called cardiomyocytes that are killed or injured in major heart attacks.

However, the heart doesn't have time to regrow these cells in major heart attacks, and replaces them with scar tissue. The heart then pumps blood less efficiently, putting more strain on the remaining healthy cardiomyocytes, leading to even less efficient pumping. This progressively disabling reaction is known as heart failure .

The goal of regenerative heart therapy is to bring in the cardiomyocytes and other cells that promote regrowth, growing them quickly enough to avoid scar tissue formation.

The scaffold approach is popular in regenerative medicine because of the three-dimensional nature of the body. The various cells of the heart and blood vessels organize themselves in specific layers. The molecular scaffolding gives a foundation for the regenerating cells to perform this self-organization.

The Lin team combined the peptide scaffold with a chemical called VEGF, or vascular endothelial growth factor , that promotes blood vessel growth. The combination attracted cardiomyocytes and other cells necessary for regrowth and improved blood supply.

The study indicated that blood circulation was improved more by enlarging already existing small arteries than by growing new blood vessels, a process known as angiogenesis. These new blood vessels turn out to be capillaries, the smallest blood vessels.

Capillaries can't increase the amount of blood delivered to a given area, Christman said; their role is to circulate the blood delivered from another region. To bring in a new supply of blood from an undamaged region of the heart, arteries are needed. The growth of arteries is called arteriogenesis.

Non-surgical treatment

The advantage of injecting the gel-like scaffolding is that it can be remotely applied, Christman wrote in her review article. The gel could be placed in the heart through a catheter threaded up the groin, the same way coronary stents are inserted into blocked vessels.

Another approach is to apply the scaffolding in a more solid patch form. This can be more precisely positioned in the heart, Christman wrote. However, it must be placed directly in the heart with surgery.

As for Ventrix, Christman said the company has begun manufacturing a clinical-grade version of its gel, suitable for use in humans.

Ventrix is located in the San Diego Science Center , a life science company incubator.