The Wall Street Journal by GAUTAM NAIK
Scientists have used nanotechnology materials to repair vital tissues damaged by heart attacks in animals, suggesting a new way to treat the same ailment in people.
The experiments, done in rats and pigs, led to the growth of fresh blood vessels and improved heart function without harmful side effects, the scientists said Wednesday in the journal Science Translational Medicine.
“Currently, there are no approved therapies in regenerative medicine for heart failure,” said Karen Christman, assistant professor of bioengineering at the University of California, San Diego, who wasn’t involved in the latest experiments. “These results are quite exciting.”
The World Health Organization estimates that more than 17 million people died from cardiovascular diseases in 2008. In the U.S., about 785,000 people will have new heart attacks this year and 470,000 will suffer recurrent ones. While more patients are surviving such events, about two-thirds don’t make complete recoveries and are vulnerable to heart failure.
Some researchers hope to treat patients by transplanting cells into the heart to promote the growth of new tissues. Animal tests have yielded promising results, and large-scale human trials are expected to kick off in coming months. But some of the early data suggest this approach may yield only small improvements in cardiac function.
An alternative technique is to deliver a protein called vascular endothelial growth factor, or VEGF, to promote blood-vessel growth in the heart. This method hasn’t worked well so far because the heart’s blood circulation tends to rapidly wash away the VEGF.
In their newly published experiments, researchers described an engineering fix for the problem. They made fibers from bits of protein and then assembled them into a lattice-like structure. Each fiber is just five nanometers wide and 100 nanometers long. (A nanometer is the length of three to six atoms placed side by side.)
The lattice structure is in the form of a sticky gel. The scientists mixed it with the VEGF and injected the combination into the hearts of two groups of test animals, rats and pigs, in which they had induced heart attacks. (Pig hearts bear significant similarities to human ones.) In both cases, instead of being washed away, the VEGF stayed on the lattice and slowly got released over several weeks.
Bone-marrow stem cells normally circulate in the blood and are part of the “repair crew” for damaged tissue. In the animal experiments, when those cells sensed the release of VEGF, they relocated to the heart and began to grow tiny blood vessels known as capillaries.
“The nanofibers create a special microenvironment in the heart for recruiting stem cells,” said Patrick Hsieh, a cardiac surgeon at the National Cheng Kung University in Taiwan and lead author of the paper.
However, fresh capillary formation isn’t enough to help a failing heart. For regeneration to continue, stem cells from both the bone marrow and the heart itself must be coaxed to grow a second layer of tissue that is necessary for the formation of arteries, which are bigger and thicker than capillaries.
To the scientists’ surprise, the prolonged release of VEGF achieved that result.
“This is the most striking finding of our approach,” said Dr. Hsieh. “We saw more than fivefold artery growth compared with the controls,” which included one group of animals that only got VEGF and another that got the nanofibers without the VEGF. The new artery growth contributed to improved heart function in the animals, Dr. Hsieh said.
The researchers also detected the creation of fresh heart muscle. This, too, is significant because the “scarring” tissue that naturally forms after a heart attack is thin and can get stretched in ways that alter the shape of the heart. In the latest experiments, the nanofiber gel appeared to strengthen these weak areas of the heart.
While the beneficial results in pig hearts were particularly important due to their resemblance to human ones, two challenges remain before the same technique can be safely attempted in people.
“We need to determine the long-term effect in animals, and we need to determine the optimal time window” when the VEGF nanofibers need to be administered, said Dr. Hsieh.
The researchers said they treated the rats and pigs immediately after a heart attack. When it comes to people, said Dr. Hsieh, it might be similarly effective to give the therapy in the first week after a heart attack, when stem-cell activity is highest.
The exact timing will now have to be pinned down. “While this therapy is promising,” said Dr. Christman, “it is important to see if the positive effect on cardiac function is maintained over the long term.”
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