Abstract
Coronary heart disease (CHD) is still one of the main causes of death in the world, despite significant advances in clinical treatments. Stem cell transplantation methods have the potential to improve cardiac function and patients' outcome following heart attack, but optimal cell types, cell preparation methods and cell delivery routes are yet to be developed. Mammalian hearts contain a small fraction of progenitor cells which, in culture, migrate out of the cardiac explants, known as explant-derived cell (EDCs) and contribute to spheroids known as cardiospheres (Csphs). Following further culture and cell passaging, Csphs give rise to cardiosphere-derived cells (CDCs). EDCs, Csphs and CDCs show in vitro and in vivo angiogenesis and tissue regeneration in myocardial ischemia. However, CDC and Csph formation is time consuming, expensive and not always successful. Therefore, this study aims to compare EDCs with CDCs and assess the effect of hypoxic preconditioning on their pro-angiogenic potential. The data showed that preconditioning EDCs in hypoxic cell culture enhances cell growth, viability and expression of stem cell and pro-angiogenic markers more than CDCs. In vivo experiments using a sub-dermal matrigel plug assay showed that EDCs and CDCs alone have limited pro-angiogenic potential; however, hypoxic preconditioning of EDCs and CDCs significantly enhances this process. Further research will increase our understanding of cardiac stem cell mediated angiogenesis and improve clinical therapies for myocardial infarction (MI) patients.
Highlights
Stem cell transplantation studies following heart attack aim to establish a way to supply adequate blood and reduce the infarct size
We showed that the expression of stem cell (Sca-1, Abcg2), endothelial and angiogenic markers (Eng, Flk1, Vegf) increased significantly in EDCs and cardiosphere-derived cells (CDCs) preconditioned with hypoxia and interestingly, this response was more significant in EDCs
Cardiac progenitors were obtained from adults C57BL/6 mice hearts and cultured in normoxia or hypoxia as described in (Amirrasouli, 2014)[11]
Summary
Stem cell transplantation studies following heart attack aim to establish a way to supply adequate blood and reduce the infarct size. Hypoxia preconditioning has been shown to stimulate numerous endogenous mechanisms such as reducing apoptosis and enhancing myocyte protection[5]. Studies have shown that hypoxia preconditioning of EDCs and CDCs markedly improves cell migration (in vitro) and cell recruitment into the ischemic myocardium[6,7,8,9,10]. We showed that the expression of stem cell (Sca-1, Abcg2), endothelial and angiogenic markers (Eng, Flk, Vegf) increased significantly in EDCs and CDCs preconditioned with hypoxia and interestingly, this response was more significant in EDCs. In order to assess the ability of CDCs and EDCs to promote neovascularization in vivo, we used a mouse model of angiogenesis with subcutaneous injection of matrigel combined with CDCs or EDCs. The results showed that EDCs and CDCs have limited angiogenic capacity alone. The results showed that EDCs and CDCs have limited angiogenic capacity alone This characteristic was significantly enhanced in both cell types upon preconditioning with hypoxia (3% O2)
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