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
‘Stem cells help produce new muscle from scar tissue after a heart attack.’
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
- 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 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.
- 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