Myocardial infarction
(MI), or heart attack, is caused by the blockage of blood flow in the heart,
which reduces oxygen levels, damages tissues (ischemia) and kills close to one
billion cardiomyocytes (infarction). Fibroblasts then migrate into the infarctedarea where they proliferate to create a cardiomyocytedepleted scar that cannotcontribute to the electrophysiologicallydriven contractions of the heart. This
often causes HF leading to fatigue, peripheral edema, or even death. To find
more effective therapies for HF, we need to improve our understanding of its
pathophysiology and develop new approaches to treating it.
Cell-replacement therapy has emerged as a
novel approach to treat HF. This approach relies on the theory that after MI or
in HF, lost cardiomyocytes can be replaced by adding either new cardiomyocytes
or a potential source of cardiomyocytes such as stem cells. To find the most
effective approach, researchers have tested several types of stem cells including
skeletal myoblasts, cardiac progenitor cells, and mesenchymal stem cells from
bone marrow. However, they have only been modestly successful because the
beneficial effects are mainly mediated by indirect paracrine mechanisms: stem
cells do not transdifferentiate into cardiomyocytes in-vivo and the number of
stem cells retained in the heart after delivery is disappointingly low.
Fortunately, cell-replacement therapy for HF using pluripotent stemcell-
derived cardiomyocytes showed more promising results in rodents and non-human
primates because they integrate and electrically couple with the healthy
myocardium. However, technologies involving stem-cell-derived cardiomyocytes
must be further optimized before they can effectively treat HF. Specifically,
we need to find methods that improve the efficiency and consistency of
cardiomyocyte differentiation in large scale, their survival in disease
conditions, their integration into cardiac tissue, and their resistance to
autoimmune rejection.
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