Cell-based cardiovascular repair and regeneration in acute myocardial infarction and chronic ischemic cardiomyopathy current status and future developments

Abstract

Ischemic heart disease is the main cause of death and morbidity in most industrialized countries. Stem-and progenitor cell-based treatment approaches for ischemic heart disease are therefore an important frontier in cardiovascular and regenerative medicine. Experimental studies have shown that bone-marrow-derived stem cells and endothelial progenitor cells can improve cardiac function after myocardial infarction, clinical phase I and II studies were rapidly initiated to translate this concept into the clinical setting. However, as of now the effects of stem/ progenitor cell administration on cardiac function in the clinical setting have not met expectations. Thus, a better understanding of causes of the current limitations of cell-based therapies is urgently required. Importantly, the number and function of endothelial progenitor cells is reduced in patients with cardiovascular risk factors and/or coronary artery disease. These observations may provide opportunities for an optimization of cell-based treatment approaches. This review provides a summary of current evidence for the role and potential of stem and progenitor cells in the pathophysiology and treatment of ischemic heart disease, including the properties, and repair and regenerative capacities of various stem and progenitor cell populations. In addition, we describe modes of stem/progenitor cell delivery, modulation of their homing as well as potential approaches to "prime" stem/progenitor cells for cardiovascular cell-based therapies.

Direct Cardiomyocyte Reprogramming: A New Direction for Cardiovascular Regenerative Medicine

“…This opened the floodgates to a number of human clinical studies and later trials testing a variety of mostly bone marrow-derived cell types in patients with both acute MI as well as chronic heart disease. These cell types include hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), umbilical cord blood stem cells, and various adult cardiac stem cells (CSCs) (Templin et al 2011) as well as skeletal muscle cells (Menasche 2008). Now that a number of these trials have been published including results from multiyear follow-up studies, a few broad lessons about cellbased therapy for the heart might be gleaned.…”

Biomaterial‐Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives

“…(72) Poor cell retention is likely to be a major factor underling the failure of cell-based therapies for MI to achieve consistent and substantial efficacy to date. (34,73) Injected cells in a saline vehicle are lost extremely quickly with the majority lost within the first 24 hours. There has been significant variability in reported rates of retention in preclinical delivery, however, most studies confirm that the vast majority of cells are lost within the first few days post -1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 administration.…”

Reprogrammed Endothelial Cells

“…Do iVPCs recruit endogenous stem or vascular progenitor cells from cardiac, bone marrow, or extracardiac vascular stem cell niches? 10 -12 [23][24][25] Thus, it will be necessary to demonstrate that iVPCs can still produce collateral growth in preclinical models of cardiovascular risk factors and disease with their associated vascular oxidative stress and endothelial dysfunction. These conditions could complicate the ability of iVPCs to differentiate, proliferate, and survive.…”