How to turn damaged heart tissue back into healthy heart muscle—new details emerge

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According to Medical Xpress


Induced cardiomyocytes (iCMs) that Li Qian’s lab produced in experiments turning scar tissue into healthy heart muscle. Credit: Qian Lab, UNC School of Medicine

Reversing scar tissue after a heart attack to create healthy heart muscle: this would be a game-changer in the field of cardiology and regenerative medicine. In the lab, scientists have shown it’s possible to change fibroblasts (scar tissue cells) into cardiomyocytes (heart muscle cells), but sorting out the details of how this happens hasn’t been easy, and using this kind of approach in clinics or even other basic research projects has proven elusive.

Now, in a new study published today in Nature, UNC researchers report a breakthrough. They have used single cell RNA sequencing technology in combination with mathematical modeling and genetic and chemical approaches to delineate the step-by-step molecular changes that occur during cell fate conversion from fibroblast to cardiomyocyte. The scientists, led by Li Qian, PhD, assistant professor of pathology and laboratory medicine at the UNC School of Medicine, not only successfully reconstructed the routes a single cell could take in this process but also identified underlying molecular pathways and key regulators important for the transformation from one cell type to another.

“We used direct cardiac reprogramming as an example in this study,” said Qian, the senior author of this paper and member of the UNC McAllister Heart Institute, “But the pipelines and methods we’ve established here can be used in any other reprogramming process, and potentially other unsynchronized and heterogeneous biological processes.”

When we are babies, embryonic stem  throughout our bodies gradually change into a variety of highly specialized cell types, such as neurons, blood cells, and . For a long time, scientists thought these specific cell types were terminal; they could not change again or be reverted back to a state between embryonic and their final differentiated stage. Recent discoveries, though, show it’s possible to revert terminally differentiated somatic cells to a pluripotent state – a kind of “master” cell that can self-produce and potentially turn into any kind of cell in the body. Scientists have also figured out how to convert one kind of differentiated somatic cell type into another without detouring through the pluripotent stage or the original progenitor stage. Such findings shifted the paradigm of cellular hierarchy and revolutionized stem cell research and the field of regenerative medicine. Yet, figuring out how to study the specifics of these processes to leverage them for clinical and basic research has been difficult.

Direct cardiac reprogramming, a promising approach for cardiac regeneration and disease modeling that the Qian Lab has pioneered and fine-tuned in the past several years, involves direct conversion of cardiac non-myocytes into induced cardiomyocytes (iCMs) that closely resemble endogenous CMs. Like any reprogramming process, the many cells that are being reprogrammed don’t do so at the same time.


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This article and images were originally posted on [Medical Xpress] October 25, 2017 at 01:03PM

Credit to Author and Medical Xpress




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