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Cell-Based Therapy of Ischemic Heart Failure

Mohamed Gaballa

Ischemic heart failure (IHF), heart failure secondary to myocardial infarction, is the number one killer in the US. Despite all the major advances in cardiac interventions, its relevance is on the rise. There is an urgent need for an effective alternative therapy. Stem cells have the potential to ameliorate many chronic illnesses such as IHF. Like any new therapy, several unanswered questions need to be addressed. The first question to be addressed is which type of stem cell should be used? There are several types of cells that have previously been investigated including embryonic stem cells, inducible pluripotent cells, and adult cells. Among the most commonly used adult cell type are fat cells, cord blood, bone marrow, cardiac cells, and myoblasts. Many cell-based strategies have been utilized, for example, one strategy has been directed differentiation of embryonic and inducible pluripotent stem cells have provided an unlimited number of cardiomyocytes for cell replacement of the lost cardiac cells in IHF. A second strategy has been exogenous stem cells may be generated and used as progenitors to regenerate the myocardium. A third strategy has been adult cardiac progenitor cells may be created by partial de-differentiation of tissue cardiac cells and delivered to regenerate the injured myocardium. The second question to be addressed is what are the mechanisms of action of these cells? This question may be complicated by the difficulty in identifying the cells’ active ingredients, effective dose, treatment duration, and specific targeted pathology. A common mechanism of action of all those strategies appears to be the paracrine factors such as growth factor or microRNA secreted by those exogenous cells. This hypothesis is supported by the findings that most cell-based therapies lead to an improvement in cardiac function with minimal structural contribution of exogenous cells’ to the damaged myocardium. This review covers the recent advancements in cell therapy such as iPSCs technology and the generation of modified adult cardiac progenitor cells. Using cells derived from bone marrow, cord blood, fat cells and others is covered in several other review articles. The third question to be addressed is what is an efficient delivery route to the targeted organ? Common cell delivery techniques are discussed in this review and more attention is given to the retrograde coronary vein delivery technique and the cardiac patch technology. Finally, the next possible phase of personalizing cell therapy is discussed, in which, gene and cell therapies are combined. With the recent advances of gene editing combined with more modern and simpler technologies, such as CRISPER/CAS9, genetically editing tissue-derived cells prior to implantation into injured hearts is quickly becoming a reality. There are many excellent review articles that have discussed additional cell delivery techniques such as systemic infusion, direct intramyocardial injection, and intracoronary artery infusion, but this review focuses on the progress in cellbased therapy for the last three years (2014-2016).