July 23, 2009
Neuregulin 1 Causes Heart Muscle Cells To Replicate

A protein called neuregulin 1 (NRG1) serves as a growth factor which when injected into mice causes muscle cells to replicate and repair damaged hearts.

Injured heart tissue normally can't regrow, but researchers at Children's Hospital Boston have now laid the groundwork for regenerating heart tissue after a heart attack, in patients with heart failure, or in children with congenital heart defects. In the July 24 issue of Cell, they show that a growth factor called neuregulin1 (NRG1), which is involved in the initial development of the heart and nervous system, can spur heart-muscle growth and recovery of cardiac function when injected systemically into animals after a heart attack.

I'm picturing people with heart disease buying this compound on the black market. Suppose it gets sold legally in any countries?

No need for embryonic stem cells or even adult stem cells. Muscle cells can be induced to start dividing.

After birth, heart-muscle cells (cardiomyocytes) normally withdraw from the cell cycle – meaning they stop dividing and proliferating. But the researchers, led by Bernhard Kühn, MD, and Kevin Bersell of the Department of Cardiology at Children's, were able to restart the cell cycle with NRG1, stimulating cardiomyocytes to divide and make copies of themselves -- even though they are not stem cells.

This makes me wonder what other adult fully differentiated post-mitotic (no longer dividing) cells in the body can be induced to start dividing again.

Ways of doing heart repair might be closer than we thought.

"Although many efforts have focused on stem-cell based strategies, our work suggests that stem cells aren't required and that stimulating differentiated cardiomyocytes to proliferate may be a viable alternative," says Kühn, the study's senior investigator and a practicing pediatric cardiologist at Children's since 2007.

Injection of neuregulin 1 (NRG1) and stimulation of production of a receptor for NRG1 caused heart muscle cell growth and improved heart function in mice.

When the team injected NRG1 into the peritoneal cavity of live mice after a heart attack, once daily for 12 weeks, heart regeneration was increased and pumping function (ejection fraction, assessed on echocardiograms) improved as compared with untreated controls. The NRG1-injected mice also lacked the left-ventricular dilation and cardiac hypertrophy that typify heart failure; both were seen in the controls.

When the researchers also stimulated production of a cellular receptor for NRG1, known as ErbB4, cardiomyocyte proliferation was further enhanced, demonstrating that NRG1 works by stimulating this receptor. They also identified the specific kinds of cardiomyocytes (mononucleated) that are most likely to respond to treatment.

Knowing how to repair our bodies as we age in very large part amounts to knowing how to instruct cells to fix everything that gets broken.

Update: Reason at the Fight Aging blog reports on another recent success in heart repair where Mayo Clinic researchers used induced pluripotent stem (iPS) cells to repair damaged hearts in mice. Because the heart is such a mechanical large sized device it seems a lot more amenable to repair than the brain or the spinal cord. I expect we'll stop suffering from heart disease before we stop suffering from strokes or dementia.

Share |      Randall Parker, 2009 July 23 11:38 PM  Aging Treatment Studies


Comments
kurt9 said at July 24, 2009 9:08 AM:

This makes me wonder what other adult fully differentiated post-mitotic (no longer dividing) cells in the body can be induced to start dividing again.

Like brains following a stroke. I am not surprised by this finding. It has been obvious to me since the late 90's that any tissue in the body should be capable of self-regeneration with the appropriate growth factors.

If you'd like, I could probably find a lab in Taiwan or China that can manufacture these growth factors.

Now that I remember, I saw a business plan for a start-up biotech in Taiwan for making various growth factor compounds. This was in 2000 when I joined the optical telecoms start-up (which crashed and burned in spring of 2001) in Taiwan.

Nick G said at July 24, 2009 10:30 AM:

I wonder, how narrowly focused is this growth factor?

How do they know this is heart-specific? Could it be stimulating growth & repair elsewhere, and the researchers weren't looking for it?

Brett Bellmore said at July 25, 2009 4:05 AM:

That's what occurred to me: Granted, cardiac muscle is a little different from regular muscle, but it wouldn't be surprising if this growth factor had effects on, at least, muscle tissue throughout the body.

Lou Pagnucco said at July 25, 2009 8:58 AM:

NRG1 also appears to be effective in several neurological disorders. For example,


Opening the Window of Opportunity: Neuregulin-1 Protects Neurons from Stroke Hours after the Event
http://www.ninds.nih.gov/news_and_events/news_articles/news_article_stroke_neuregulin.htm

Excerpt -
"Neuregulin-1 protected neurons from damage even when administered as long as 13 ½ hours after the stroke's onset. At that point it protected 60 percent of the neurons,” says Dr. Ford. “Even two weeks after a single injection of neuregulin-1 we still saw no increase in the damage. The increased time period that neuregulin-1 is able to protect neurons after stroke would be a great benefit to stroke patients.”


I wonder how many hospitals or clinics have adopted this therapy.

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