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Reversing a heart attack: scientists reprogram scar tissue into working muscle

The views expressed are those of the author and are not necessarily those of Scientific American.


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Cardiovascular disease is the world’s leading cause of death. Approximately every 25 seconds, an American has a heart attack. One of the vessels to the heart gets blocked, cutting off blood flow to part of the heart. Then, the starving tissue begins to die, causing pain in the chest and difficulty breathing and, eventually, death. Every minute, someone in America dies from one of these coronary events. Those that survive the attack are still at risk for future problems as dead heart muscle leads to scar tissue that weakens the heart and increases the chance of heart failure. Until now, there was little that could be done for them, other than to encourage healthy lifestyle practices.

Just this week, Gladstone researchers announced a major breakthrough in heart disease research: they successfully reprogrammed scar tissue in live mice back into functional heart muscle.

A mouse heart a month after a heart attack - scar tissue appears white

The researchers were able to use a virus-based system to deliver three key genes that guide embryonic heart development—Gata4, Mef2c and Tbx5 (GMT)—to areas of mouse hearts that were damaged in a heart attack. Within a month, cells that normally became scar tissue were beating away again as if they were not knocking on death’s door just 30 days before. By the three month mark, treated mice showed marked improvements in cardiac functioning.

“The damage from a heart attack is typically permanent because heart-muscle cells—deprived of oxygen during the attack—die and scar tissue forms,” said Dr. Deepak Srivastava, director of cardiovascular and stem cell research at Gladstone. “But our experiments in mice are a proof of concept that we can reprogram non-beating cells directly into fully functional, beating heart cells—offering an innovative and less invasive way to restore heart function after a heart attack.”

“This research may result in a much-needed alternative to heart transplants—for which donors are extremely limited,” said lead author Dr. Li Qian, a post doc at the California Institute for Regenerative Medicine. But the best part is that this method would use the person’s own cells, removing the need for stem cells or donor hearts. “Because we are reprogramming cells directly in the heart, we eliminate the need to surgically implant cells that were created in a petri dish.”

“We hope that our research will lay the foundation for initiating cardiac repair soon after a heart attack—perhaps even when the patient arrives in the emergency room,” said Srivastava. The ability to regenerate adult heart tissue from its own cells is a promising approach to treating cardiac disease because it may face fewer obstacles to clinical approval than other approaches. However, there is much to be done before this breakthrough becomes a treatment. “Our next goal is to replicate these experiments and test their safety in larger mammals, such as pigs, before considering clinical trials in humans.”

Previous work has been able to do this kind of cellular reprogramming in cultured cells, but clinically it is much more efficient if a treatment can work directly on live hearts. In 2010, coronary heart disease was projected to cost the United States $108.9 billion, including the cost of health care services, medications, and lost productivity. If research such as this can lead to improved functioning after a heart attack, it could save millions in health care costs, not to mention potentially save lives by preventing heart failure down the line. While this research’s implications for heart disease treatment is clear, this kind of in vivo reprogramming may be also useful in a variety of other diseases where tissue damage is a major cause of symptoms, including Alzheimer’s and Parkinson’s disease.


A normal and reprogrammed heart cell beating eight weeks after a heart attack

Reference: Qian, L. et al. 2012. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytesNature DOI:10.1038/nature11044

Christie Wilcox About the Author: Christie Wilcox is a science writer and blogger who moonlights as a PhD student in Cell and Molecular Biology at the University of Hawaii. Follow on Google+. Follow on Twitter @NerdyChristie.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. IncredibleMouse 8:04 pm 04/18/2012

    I would love to read the research, protocols and methods that went into this. Fascinating. If there were ever any objections to the use and research of viral vectors as a delivery vehicle for custom genetic code, they’ve got to be squashed now, right? I do feel a bit bad for these and other scientists though.. any benefits to humans will just be miracles attributed to respective deities.

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  2. 2. checkmate4u 9:32 pm 04/18/2012

    No, viral vectors are still in the infant stages of research and development. It is possible to outfit a common retrovirus with, how you put it, “custom genetic code,” and subsequently inject it into a group of cultured cells,but only in vitro, because the possibility of the virus inserting the genetic material into the wrong place is very real. So, you don’t want this to happen in vivo and cause an oncogene to go berserk or something.

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  3. 3. JamesDavis 7:38 am 04/19/2012

    What is this about ten years away from becoming reality; I may not last that long? Will the method also work on old scar tissue?

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  4. 4. scholfield 9:24 am 04/19/2012

    This is indeed an impressive study and represents a milestone in ‘stem cell’ research. Nevertheless, when eventually this becomes a viable treatment, it will need a long stay in intensive care and its cost will be beyond the means of most people and health care services around the world. A far more cost effective approach is life-style changes long before the vessels become blocked. This seems to be the explanation of a 50% reduction in myocardial disease in the southern UK (but not in other areas of the UK). Such behavioural changes also benefit vascular function in other tissues, especially the kidney and brain where similar repair strategies would be even more difficult. In translation from 12 week old mice or pigs to fat old humans, there is a major hurdle in that potential progenitor cells or fibroblasts are themselves dysfunctional and may not transdifferentiate. For example, one of the causes of vascular disease is the failure of circulating endothelial progenitor cells to replace endothelial damage which causes the ‘heart attack’. Lastly, the myocardial vascular disease also needs fixing otherwise ‘heart failure’ will be repeated in other parts of the heart. Thus, this is a potential solution to repair but not tackling the root cause of the damage – vascular disease.

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  5. 5. pknoepfler 1:25 pm 04/19/2012

    Great piece, Christie. I provide my own take on this as a stem cell biologist here. http://tinyurl.com/d63kht2. Safety is a concern for example. James, you are right that this is about a decade out at least from the bedside and older cells are somewhat less receptive to reprogramming, but in theory this could work for already injured/scarred hearts. Keep hope!

    Paul

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  6. 6. gmperkins 3:54 pm 04/19/2012

    That appears to be some great work by Gladstone. I would have never considered “turning the cells back on” as a possible treatment for damaged heart tissue.

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