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MicroRNAs Repair Heart Damage
Earlier this year, it was shown that some of the damage caused by a heart attack could be repaired by giving patients an injection of their own stem cells. Now, researchers from Duke University have done the same by injecting tiny molecules of RNA known as microRNAs.
Because microRNAs are so small, they can be made synthetically, which makes them a much better candidate for therapy than stem cells, which much first be isolated from a patient and then grown up in the laboratory.
Much of the damage from a heart attack comes from the death of heart muscle tissue, which is replaced by scar tissue. Scar tissue is something like a patch; it's never as functional as the tissue it replaces. In the heart, scar tissue can't contract and beat like heart muscle tissue can. And with less muscle, the heart can no longer pump blood as well as it did before the heart attack. But it might if the scar tissue could be turned back into muscle tissue. Which is what the Duke scientists appear to have accomplished in mice.
MicroRNAs were first discovered in 1993. They essentially turn off (silence) genes without interacting with the genes themselves. They attach to the initial gene product (messenger RNA), inactivating it and halting the production of protein that would normally follow.
In this case, silencing specific genes in scar tissue causes it to transform into muscle tissue.
Based on the known effects of specific microRNAs, the researchers selected several to test singly and in combination on cells known as fibroblasts. Fibroblasts are the cells that make up most of connective tissue, which is what scar tissue is. Using fibroblasts grown in laboratory dishes, the researchers found that several microRNAs had the ability to turn them into a cell type that strongly resembled muscle cells. The combination of four separate RNAs given together -- miRNAs 1, 133, 208 and 499 -- was the most effective at producing this transformation.
They then tested this combination on mice with damaged hearts and found that much of the scar tissue was converted into tissue that seems indistinguishable from normal heart muscle. The study did not test the ability of this change to restore heart function back to its pre-damage level.
It wasn't long ago that scar tissue was thought to be permanent. Though that's now known not to be true, the science of turning scar tissue back into healthy tissue is still in its infancy. Studies are now planned to see if microRNAs can repair heart damage in larger animals. If they can, the researchers think that therapies in humans might begin within a decade.
If the technique pans out, its uses will likely extend way beyond the heart. As the researchers point out: "If you can do this in the heart, you can do it in the brain, the kidneys, and other tissues. This is a whole new way of regenerating tissue."
An article on the study was published online by Circulation Research.
June 16, 2012