ABSTRACT
Introduction The mammalian heart has a very limited capacity to regenerate lost cardiomyocytes. Consequently, extensive cardiomyocyte loss (e.g. due to infarction or myocarditis) typically heals by scar formation, which leaves the patient with a contractile deficit that often progresses to heart failure. Prompted by the clinical need to treat heart failure, scientists in the mid1990s began exploring cell-based cardiac repair in an attempt to remuscularize damaged hearts. Shortly thereafter, researchers in adult stem cell biology advanced the notion of stem cell plasticity, which suggested that adult stem cells could differentiate into unexpected cell types (transdifferentiate) when placed into a new tissue environment.1 Since that time, many studies have examined the ability of adult stem cells to form new cardiomyocytes or other myocardial cells, and, encouragingly, physiological studies consistently show improved contractile function following transplantation of adult stem cell derivatives (reviewed below). The goal of this chapter is to provide a critical review of the evidence that extracardiac progenitor cells form new myocardium in vitro and in the mammalian heart in vivo. Due to the large body of literature on this topic, we will spend a
significant portion covering bone marrowderived stem cells in this chapter. We recommend the reader to refer to Chapter 6 by Professor Doevendans and colleagues on resident cardiac progenitor cells and Chapter 5 by Professor Kloner and Dr Dai for a more in-depth analysis of mesenchymal stem cells.
