Abstract

Myocardial infarction is a leading cause of death globally due to the inability of the adult human heart to regenerate after injury. Cell therapy using cardiac-derived progenitor populations emerged about two decades ago with the aim of replacing cells lost after ischaemic injury. Despite early promise from rodent studies, administration of these populations has not translated to the clinic. We will discuss the need for cardiac regeneration and review the debate surrounding how cardiac progenitor populations exert a therapeutic effect following transplantation into the heart, including their ability to form de novo cardiomyocytes and the release of paracrine factors. We will also discuss limitations hindering the cell therapy field, which include the challenges of performing cell-based clinical trials and the low retention of administered cells, and how future research may overcome them.

Highlights

  • Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide (WHO)

  • Transplantation of embryonic stem cell (ESC)-derived ISL1+ progenitors improved cardiac function following MI demonstrating the validity of transplanting developmental cardiac progenitors with the aim of replacing lost cardiomyocytes [79]

  • Smart et al [95] showed that Wilms tumour 1 (WT1)+ progenitors transplanted into infarcted hearts formed de novo cardiomyocytes, the contribution of Epicardium-derived cells (EPDCs) to both vasculature and cardiomyocytes was insufficient for effective myocardial regeneration

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Summary

Introduction

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide (WHO). Several cell populations including stromal cells, such as mesenchymal stem cells, and cardiac progenitor cells (CPCs) have been investigated for transplantation with the aim of replacing lost cells following MI. ISL1+ progenitors have been shown to contribute to the formation of cardiomyocytes, endothelial cells and smooth muscle cells [77].

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