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Journal of Biomedical Research | Volume: 29
4th World Heart Congress
Molecular Biology, Tissue Science and Regenerative Medicine
International Conference on
Joint Event
&
November 19-20, 2018 | Paris, France
Challenges to the application of stem-cell therapy for
treatment of cardiac disease include isolation and safe,
stable long-term integration of cells. Stem cell isolation,
delivery, survival and proliferation in host tissues have been
the focus of many studies, but concerns about the long-term
electrochemical integration and safety of implanted cells have
been largely neglected. We have also published studies focused
on enhancing the survival of MSCs transplanted in the harsh
pathologic conditions of infarcted myocardium. However,
we have found that improved MSC transplantation does not
provide a proportional survival benefit that is compatible
with a significant improvement in cardiac contractile function.
One possible explanation for this discrepancy is that the focal
application of MSCs that have not differentiated into electrically
functional cardiomyocytes creates fixed heterogeneity between
host tissues in the engrafted region, possibly predisposing the
heart to ventricular arrhythmia. A previous report described the
trilineage differentiating capacity of MSCs after implantation in
an infarcted heart, but we have observed that MSCs do not
differentiate into cardiomyocytes, at least not during the early
phase after myocardial infarction, when the risk of sudden
arrest or death is highest. Transplantation of undifferentiated
MSCs seems to attenuate their beneficial effects and thus
impede their ability to prevent sudden arrhythmic death. We
concluded, therefore, that naïve MSCs are not optimal cells
for cardiac regeneration in clinical settings and determined
that MSCs must be modified before transplantation to possess
cardiogenic properties and the ability to electromechanically
integrate with the host myocardium. Inexcitable properties of
undifferentiated MSCs contribute to decreases of conduction
velocity, increasing the susceptibility to ventricular arrhythmia
and leading to sudden death. In order to obtain a cardiogenic
cell type capable of electromechanically integrating with host
tissue for cardiac regeneration, we induced differentiation of
MSCs with protein kinase C activation. We show that small
molecules, including kinase inhibitors, can change the fates
of stem cells in recognizable ways and that a protein kinase C
(PKC) activator, phorbol myristate acetate (PMA), induces the
expression of cardiogenic markers. This approach provides a
new strategy in cell-based therapy for myocardial infarction
that may prevent fatal arrhythmia and mortality and improve
contractile function.
Speaker Biography
Ki-Chul Hwang is vice-president and professor of College of Medicine, Catholic
Kwandong University and director at Institute for Bio-Medical Convergence,
International St. Mary’s Hospital of Korea. He received his doctor of philosophy
degree from the Korea University in Republic of Korea and completed his postdoctoral
fellowship at the Cleveland Clinic Foundation, Cleveland, OH, USA and the Victor
Chang Cardiac Research, NSW University, Sydney, Australia. He has consecutively filled
(Senior) editorial board at the World Journal of Stem Cells, American Journal of Stem
Cells and Journal of Geriatric Cardiology. Much of his research career has focused on
the adult stem cells and he is recognized to be at the forefront of the emerging field
about functional enhancement in stem cells and its therapeutic role associated with
many diseases.
e:
Ki-Chul Hwang
Catholic Kwandong University, South Korea
More insights into mesenchymal stem cells as therapeutics
Ki-Chul Hwang, Molecular Biology & Heart Congress 2018, Volume 29
DOI: 10.4066/biomedicalresearch-C8-021