Content area
Full text
Arianna Mauretti [1; 2] and Sergio Spaans [1; 2] and Noortje A. M. Bax [1; 2] and Cecilia Sahlgren [1; 2; 3; 4] and Carlijn V. C. Bouten [1; 2]
Academic Editor: Sari Pennings
1, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, Netherlands, tue.nl
2, Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands, tue.nl
3, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland, abo.fi
4, Turku Centre for Biotechnology, Åbo Akademi University and University of Turku, 20520 Turku, Finland, btk.fi
Received Mar 31, 2017; Accepted Jul 26, 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Cardiac tissue is a composite material consisting of contractile and supportive cells surrounded by extracellular matrix (ECM) and is intertwined with nervous and vascular networks. An ischemic event, such as a myocardial infarction (MI), not only induces cell death but also affects the tissue structure and composition. This can eventually lead to loss of cardiac function due to changes in the key players of the cardiac microenvironment: (1) stem/progenitor cells and supporting cells, (2) extracellular matrix (ECM) proteins, (3) the mechanical environment of the cells and the matrix, such as the cyclic strain provided by the beating heart, and (4) soluble factors, such as oxygen and cytokines (Figure 1(a)). In this review, we omit to describe vascular components, innervation, and electrical conduction, as these are extensively reviewed elsewhere [1–3], although their derivatives, such as oxygen gradients and cyclic strain, are included.
[figure omitted; refer to PDF]
The myocardium shows very limited self-renewal; nevertheless, the notion of the heart as a terminally differentiated organ, incapable of regenerating after injury, has been challenged by abundant evidence in the last decade [4, 5]. There is ongoing debate over whether cardiac regeneration is to be attributed to dedifferentiation and proliferation of cardiomyocytes [6, 7] or to differentiation of cardiac stem or progenitor cells [8–10], which makes it difficult to identify the ideal therapeutic target. Nevertheless, the existence of resident cardiac progenitor cells (CPCs) in the heart and their relevance for cardiac regeneration have been demonstrated...