The Role of Antioxidation and Immunomodulation in Postnatal Multipotent Stem Cell-Mediated Cardiac Repair

Abstract

Oxidative stress and inflammation play major roles in the pathogenesis of coronary heart disease including myocardial infarction (MI). The pathological progression following MI is very complex and involves a number of cell populations including cells localized within the heart, as well as cells recruited from the circulation and other tissues that participate in inflammatory and reparative processes. These cells, with their secretory factors, have pleiotropic effects that depend on the stage of inflammation and regeneration. Excessive inflammation leads to enlargement of the infarction site, pathological remodeling and eventually, heart dysfunction. Stem cell therapy represents a unique and innovative approach to ameliorate oxidative stress and inflammation caused by ischemic heart disease. Consequently, it is crucial to understand the crosstalk between stem cells and other cells involved in post-MI cardiac tissue repair, especially immune cells, in order to harness the beneficial effects of the immune response following MI and further improve stem cell-mediated cardiac regeneration. This paper reviews the recent findings on the role of antioxidation and immunomodulation in postnatal multipotent stem cell-mediated cardiac repair following ischemic heart disease, particularly acute MI and focuses specifically on mesenchymal, muscle and blood-vessel-derived stem cells due to their antioxidant and immunomodulatory properties.

Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction

“…As the Bio-Plex assay revealed, BMSCs cultured in hypoxia, compared to those cultured in normoxia, released significantly less pro-inflammatory cytokines (TNF-α, GM-CSF), more anti-inflammatory cytokines (IL-6, IL-10), and less pro-fibrotic cytokine (TGF-β1). Of particular interest, our data confirmed that hypoxic condition potentiated the production VEGF as it was also evidenced elsewhere [35, 36]. However, the inflammation network and cytokine cascades in myocardial infarction might, in fact, elaborate temporally and spatially in a complicated and dynamic pattern [32].…”

A single injection of protein-loaded coacervate-gel significantly improves cardiac function post infarction

“…Large amounts of reactive oxygen species produced by inflammatory cells invading the infarcted myocardium can cause massive cell death [49]. The spatiotemporal delivery approach employed in our study proved effective at reducing inflammation and promoting tissue repair.…”

Towards comprehensive cardiac repair and regeneration after myocardial infarction: Aspects to consider and proteins to deliver

“…Inflammatory cells can promote beneficial effects such as inducing angiogenesis by monocytes secreting proangiogenic factors and phagocytosis of dead cells and their cellular debris. However, they can also have detrimental effects on cell survival and cause tissue damage, infarct expansion, and LV dilation [60, 61]. Neutrophils produce large amount of reactive oxygen species (ROS) and elastase which cause cell apoptosis and elastin degradation [61, 62].…”

“…However, they can also have detrimental effects on cell survival and cause tissue damage, infarct expansion, and LV dilation [60, 61]. Neutrophils produce large amount of reactive oxygen species (ROS) and elastase which cause cell apoptosis and elastin degradation [61, 62]. In addition, they can reduce the proangiogenic effects of progenitor cells and bolster ischemic conditions [63, 64].…”

“…Proinflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and IL-1 levels are elevated in the infarct zone and activate matrix metalloproteinases (MMPs), which degrade the ECM(Table 1) [61]. For example, leukocyte-derived MMP-9 deletion protects the ischemic heart from LV dilation and cardiac rupture, but also disrupts angiogenesis [66].…”