The Challenges for Cardiac Vascular Precursor Cell Therapy: Lessons from a Very Elusive Precursor

Abstract

There is compelling evidence that cardiovascular disorders arise and/or progress due mainly to endothelial dysfunction. Novel therapeutic strategies aim to generate new myocardial tissue using cells with regenerative potential, either alone or in combination with biomaterials, cytokines and advanced monitoring devices. Among the human adult progenitor cells used in such methods, those historically termed ‘endothelial progenitor cells' show promise for vascular growth and repair. Asahara et al. [Science 1997;275:964-967] initially described putative endothelial cell precursors in 1997. Subsequently, distinct cell populations termed endothelial colony-forming units-Hill, circulating angiogenic cells and endothelial colony-forming cells were identified that varied in terms of phenotype, vascular homeostasis contribution and purity. Notably, most of these cells are not genuine vascular precursor cells belonging to the endothelial lineage. This review provides a broad overview of the main properties of the endothelium, focusing on the basis governing its growth and repair. We discuss efforts to identify true vascular precursors, a matter of debate for the past 15 years, as well as recent methodological advances in identifying new hierarchies of more homogeneous, clonogenic and proliferative vascular endothelial-lineage precursors. Consideration of these issues provides insights that may help develop more effective therapies against human diseases that involve vascular deficits.

Classification of New Biomarkers of Dilated Cardiomyopathy Based on Pathogenesis—An Update

“…EPCs are bone marrow derived cells, which are increased in response to vascular injuries through mediators such as VEGF-A and SDF-1 [73]. Studies have reported elevated EPCs level in DCM patients and have further been confirmed by Theiss et al who showed raised level of CD34+ cells in DCM patients as compared to normal population [74].…”

Fibrin, the preferred scaffold for cell transplantation after myocardial infarction? An old molecule with a new life

“…Enormous research efforts have been focused on increasing the repair and regeneration of functional myocardial tissue, including approaches based on the administration of cells with regenerative capacity (cellular cardiomyoplasty) (Orlic et al , ; Kuhbier et al , ; Hoke et al , ; Behfar et al , ; Taylor and Robertson, ; Taylor, ). However, although preliminary reports in rodents and pigs have provided proof‐of‐concept data for most methods of regenerating damaged cardiac tissue (Tomita et al , ; Barbash et al , ; Bayes‐Genis et al , ; Alestalo et al , ; Song et al , 2014), the clinical results are not as solid or conclusive (Assmus et al , ; Cleland et al , : Strauer and Steinhoff, ; Roura et al ., ; Gyöngyösi et al , ). Major challenges are posed by the requirements for an efficient delivery system and the survival of large numbers of cells within the injured heart (Chachques et al , ; Soler‐Botija et al , ).…”

Mesenchymal stem cells for cardiac repair: are the actors ready for the clinical scenario?

“…As mentioned previously, most efforts in the field of cardiac regeneration after MI have focused on cell therapy. Clinically, the vast majority of reported studies, mostly using bone marrow-derived mononuclear cells (revised in [ 41 ]), are intricate to compare because the delivered cells are either mixed or enriched populations, and the number of implanted cells, delivery methods, and injection time intervals are not usually comparable. Other experiences have included MSCs harvested from bone marrow aspirates [ 42 , 43 ], subcutaneous adipose tissue [ 44 ], and Wharton’s jelly [ 45 ].…”