Can Scar Tissue After a Heart Attack be Turned Back into Functioning Heart Muscle?

Highlights:

• After a heart attack the dead muscle of the heart is replaced by scar tissue - stem cell can help form new muscle from the scar tissue
• Heart muscle called cardiomyocytes are being produced from scar tissue (fibroblasts) using different techniques
• These vary genetically according to the technique used to produce them

Scientists compared reprogrammed cardiomyocytes produced by two different techniques – the iPSC-CMs and iCMs. They published their study in Cell Reports. Following a heart attack, the muscle cells of the heart, referred to as cardiomyocytes, die in the affected area. The cells of the heart, like those of the brain, are unable to regenerate. This weakens the heart muscle which is then unable to carry out its pumping function efficiently and a large damaged area can result in heart failure.

In the recent years, attempts have been made to regenerate the heart cells, which can then be used to replace the damaged cardiac muscle. In addition, the muscle cells thus produced can be used for other purposes like disease modeling and drug screen. In disease modeling, a model of the heart muscle is created in the laboratory to study pathological processes associated with the disease. A drug screen that uses the cells from a patient could help to determine the drugs and dosage that would work best for that particular patient.

Two approaches have been used to develop functional cardiomyocytes from fibroblasts, cells that normally produce fibrous or scar tissue.

• The fibroblasts are first converted into induced pluripotent stem cells (iPSCs), an immature form of cells, which then differentiate into cardiomyocytes. This process partially resembles the normal development of heart cells during embryonic development.
• The fibroblasts are directly reprogrammed into induced cardiomyocytes (iCM)

Scientists compared the cardiomyocytes produced by the two procedures. They found that:

• Differences were observed in the expressed genes as well as a large number of noncoding RNAs in the cardiomyocytes produced by the different procedures.
• When the genes that were activated and not activated in the cells were compared, the iPSC cardiomyocytes (iPSC-CMs) were more similar to early embryonal cardiomyocytes with more active genes and a higher number of genes likely to be either activated or repressed. iCMs on the other hand, resembled adult cardiomyocytes more closely.
• The structure of the muscle cells was less organized and the contractility of the cells was less in the iPSC-CMs as compared to iCMs, reflecting the immaturity of the iPSC-CMs as compared to the iCMs.
• Longer culture times did improve the maturity of the iPSC-CMs but not as much as that of the iCMs.
• The cells differed in the genes responsible for metabolism. iPSC-CMs primarily expressed the glycolysis pathway genes, whereas iCMs primarily expressed the fatty acid oxidation genes.

These differences in the cardiomyocytes could enable scientists to understand the pros and cons of the cardiomyocytes produced by different procedures. Thus, they can determine their preference when it comes to using the cardiomyocytes for different purposes like disease modeling, drug screen, or repair of the heart muscle. Considering the immaturity of the iPSC cardiomyocytes, these cells could prove more useful for studying congenital heart diseases heart diseases that are present since birth. Since the ability to regenerate appears less in the iCMs as compared to iPSC cardiomyocytes, they could be less preferred in the regeneration of heart tissue.

Reference:

1. Yang Zhou, Li Wang, Ziqing Liu, Sahar Alimohamadi, Chaoying Yin, Jiandong Liu, Li Qian3,'Correspondence information about the author Li Qian. Comparative Gene Expression Analyses Reveal Distinct Molecular Signatures between Differentially Reprogrammed Cardiomyocytes. Cell Reports. DOI: http://dx.doi.org/10.1016/j.celrep.2017.09.005

Source-Medindia