Cardiac Progenitor Cells in Basic Biology and Regenerative Medicine

Abstract

Major cardiovascular events including myocardial infarction (MI) continue to dominate morbidity rates in the developed world. Although multiple device therapies and various pharmacological agents have been shown to improve patient care and reduce mortality rates, clinicians and researchers alike still lack a true panacea to regenerate damaged cardiac tissue. Over the previous two to three decades, cardiovascular stem cell therapies have held great promise. Several stem cell-based approaches have now been shown to improve ventricular function and are documented in preclinical animal models as well as phase I and phase II clinical trials. More recently, the cardiac progenitor cell has begun to gain momentum as an ideal candidate for stem cell therapy in heart disease. Here, we will highlight the most recent advances in cardiac stem/progenitor cell biology in regard to both the basics and applied settings.

Strategies and Challenges to Improve Cellular Programming-Based Approaches for Heart Regeneration Therapy

“…IPSC-derived CMs have also been shown to integrate into infarcted guinea pig heart, improving cardiac function and suppressing arrhythmias [ 13 ]. Human iPSC-derived cardiovascular progenitors have been successfully tested more recently in preclinical studies of canine and porcine MI models [ 14 ].…”

Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials

“…However, there is still no reliable therapy for acute cardiac conditions like myocardial infarction (MI), which account for nearly half of all cardiovascular deaths in the industrialized world [1,2]. Regenerative medicine-based strategies for infarcted myocardium have shown promise in preclinical animal models as well as early clinical trials [3]. Whilst these have demonstrated some physiological improvements in ventricular function, they were associated with very low cell retention after some weeks, suggesting a paracrine effect of transplanted cells rather than functional integration within the damaged tissue [4].…”

“…Several studies have demonstrated that the cells generated from CPCs, particularly cardiomyocytes, display an immature phenotype similar to that of embryonic cardiac cells [3]. However, when the CPCs are transplanted into a host environment, the differentiated cells reach a more advanced maturity, such as greater organisation of sarcomeres and formation of gap junctions (in the case of cardiomyocytes) and development of tubular-like structures (for smooth muscle and endothelial cells) [11,24,27,28].…”

“…Furthermore, the populations of CPC-derived cells are heterogeneous and frequently represent immature cells, which could potentially lead to arrhythmias, lower long-term stability and poor integration when transplanted [3,300]. The mechanisms involved in cardiac lineage subtype specification will need to be fully investigated and optimised to produce purer and more mature populations of the desired cell types from the CPCs.…”

CPCs and ECM: A Good Mix for Cardiac Regeneration

“…In this context, also CPCs-derived exosomes are able to exert, once released in the extracellular microenvironment, positive therapeutic effects through multiple mechanisms interacting with different target cells, such as endothelial cells and cardiomyocytes [72][73][74] . Overall, despite all these encouraging results many critical issues, including the challenges of electrical coupling, undetermined mechanism aspects and, above all, the long term engraftment and survival of injected cells, should be addressed before CPCs could be considered as a strong therapeutic tool for regenerative medicine applications [75] .…”