Javier Benitez

Introduction: Myocardial Infarction (MI) is a major public health problem that results in cardiac remodeling and resulting impaired heart function. Current treatment aims to prevent maladaptive pathways, but not seek to compensate for the loss of myocardium¹_. The use of Mesenchymal Stem Cells (MSCs) has proven to be a beneficial therapy to prevent pathological remodeling of the cardiac tissue though various mechanisms, such as angiogenesis^2-5 paracrine stimulation^3-6, and to a lesser extent, differentiation into cardiomyocytes, and activation of endogenous cardiac stem cells⁵. Methods: MSCs were transduced to overexpress CXCR4³ (MSC^CX4) and HIF-1α² (HIF-MSC) in different experiments. In addition, Nuclear casein kinase and cyclin-dependent kinas substrate (KNUCKS) knockout MSCs (NUCKS^-/- MSCs) were collected under hypoxic conditions and assessed both with molecular techniques (Western Blot, real time PCR), and histological staining with trichome stain⁴. Aside from transplanted MSCs and cultivated MSC media, delivery of MSCs via pericardial-stem cell-loaded patches was performed⁵, as well as the direct action of coculture of BMSCs with cardiomyocytes⁶. Results: HIF-MSCs showed a higher content of Jagged1 loaded exosomes (vesicles loaded with biological material), which is primordial in the NOTCH signaling pathway (which among its many actions, coordinates angiogenesis), as well as expression of miRNA-31². MSC^CX4 also showed an increase in the number of tube-like structures via paracrine stimulation with VEGF³; in addition, MSC^CX4 medium played an important role in mobilization of MSC toward ischemic tissue, as well as induced proliferation of adult rat cardiomyocytes³. NUCKS ^-/- MSCs had angiogenic effects via VEGF and IL-10; and also, showed cardio protective roles by inhibiting apoptosis of ischemic cardiomyocytes⁴. MSCs delivered via pericardial patches showed activation of epicardial cells Wt1 which have potential to differentiate further into endothelium, VSM, and cardiomyocytes; in addition, the levels of c-kit⁺ cells was also increased⁵_. Coculture of BMSCs with cardiomyocytes, inhibited the hypertrophic growth of cardiomyocytes mainly by the heightened release of VEGF⁶. Conclusion: Studies have shown that MSCs have the potential to reduce the ischemic area after a myocardial infarction by stimulation of angiogenesis, as well as supportive paracrine stimulation. Overall these actions resulted in enhanced contraction of the left ventricle as well as increased ejection fraction when compared to control groups⁵. In addition, the infarction size was reduced, and the thickness of the ventricular wall was increased, with further prevention of malignant hypertrophy; ultimately, all these events result in an enhancement of cardiac contractility^3-5.

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