The hypoxic microenvironment of stem cells and their progenies of the heart

Cardiovascular disease is a major cause of lifelong disability and the most common form of heart disease is ischaemic heart disease, characterized by an imbalance between myocardial oxygen supply and its demand. This can lead to disturbances in impulse formation and conduction in the heart in the form of arrhythmias. During myocardial infarction, a sustained ischaemia leads to irreversible necrosis of the heart muscle and a plethora of stem cell therapies have been investigated to treat cardiovascular disease.1,2 Several studies testing the regenerative potential of stem cells to treat cardiovascular disease in humans have focused on designing the optimal microenvironment for these cells.3 Based on their potency, stem cells of the heart can be divided as: i) totipotent; ii) pluripotent, such as “embryonic stem cells” (“ESCs”) and “induced-pluripotent stem cells” (“iPSCs”); iii) multipotent, such as “hematopoietic stem cells” (“HSCs”) and “mesenchymal stem cells” (“MSCs”); and iv) unipotent, such as “cardiac stem cells” (“CSCs”).3 Lastly, other progenitor cells of the heart can be identified, such as “skeletal myoblasts” (also referred to as “skeletal muscle satellite cells”) and “mesodermal VEGFR2+ cardiac progenitor cells”.3 For regenerative therapy purposes, several stem cell types and progenies at different developmental stages have been considered for transplantation into the ischemic and hold promise for future studies aiming at regenerate the heart in cardiovascular disease patients as described in this review.