Generation of induced cardiac progenitor cells via somatic reprogramming

Abstract

It has been demonstrated that cardiac progenitor cells (CPCs) represent a more effective cell-based therapy for treatment of myocardial infarction. Unfortunately, their therapeutic application is limited by low yield of cell harvesting, declining quality and quantity during the ageing process, and the need for highly invasive heart biopsy. Therefore, there is an emerging interest in generating CPC-like stem cells from somatic cells via somatic reprogramming. This novel approach would provide an unlimited source of stem cells with cardiac differentiation potential. Here we would firstly discuss the different types of CPC and their importance in stem cell therapy for treatment of myocardial infarction; secondly, the necessity of generating induced CPC from somatic cells via somatic reprogramming; and finally the current progress of somatic reprogramming in cardiac cells, especially induced CPC generation.

Keywords: CPC; cardiac progenitor cell; induced CPC; somatic reprogramming.

Figure 1. Timeline of the discovery of CPCs and their applications

A. Timeline of the discovery of different populations of CPCs. B. Timeline of the pre-clinical studies of CPCs. C. Timeline of the clinical studies of CPCs. CPC: cardiac progenitor cell; MI: myocardial infarction; IR: ischemia reperfusion.

Figure 2. Potential mechanisms of stem cell therapy for myocardial infarction

The potential mechanisms have been proposed as direct cardiac differentiation (cardiomyocytes, endothelial cells and smooth muscle cells), paracrine effects (immune regulation, gene transfer, angiogenesis cytokines, anti-apoptosis cytokines, anti-inflammation cytokines, MMP, collagen deposit), and cell fusion. CPC: cardiac progenitor cell; BMSC: bone marrow stem cell; MSC: mesenchymal stem cell; EPC: endothelial progenitor cell; MMP: matrix metalloproteinase. Dash lines indicate that the evidences are controversial.