Cardiac resident progenitor cells: evidence and functional significance

Abstract

This editorial refers to ‘Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium’, by M.Y. Emmert et al. , doi:10.1093/eurheartj/ehs156 It has been estimated that a serious myocardial infarction (MI) results in the loss of ∼1 billion functional cardiomyocytes, which are replaced with a fibrous scar, frequently leading to heart failure. Experimental data demonstrate that the mitotic renewal in the human myocardium exists but at a very low rate: 1% annually at the age of 25 and 0.45% at the age of 75.1 With this turnover rate, most cardiomyocytes will never be exchanged during a normal life span. Although the renewal rate may increase somewhat after injury, the heart itself is not able to effect large-scale cardiac regeneration. Thus, stem cell-based therapy may be a realistic strategy for providing a source of new functional cardiomyocytes. Additionally, stem cells may promote tissue healing through paracrine mechanisms. Regenerative stem cells may be derived from extracardiac sources as well as from the heart itself. Over the past decade, extensive studies have provided us with evidence that progenitor cells are present in the adult heart. In mice, cells expressing the stem cell factor receptor c-Kit,2 stem cell antigen-1 (Sca-1),3 and transcription factor islet-1 (Isl-1),4 as well as side population (SP) cells5 have been identified as cardiac resident progenitor cells (CRPCs) due to their ability to differentiate into cardiomyocytes both in vivo and in vitro . Following the animal studies, a series of studies by several independent groups have suggested that CRPCs also exist in adult or postnatal hearts of humans ( Figure 1 ),4,6–9 which are also identified by the expression of c-Kit, Sca-1, and Isl-1. In addition, cardiospheres cultured from human heart biopsies contain CRPCs and can proliferate in vitro (not addressed in …