Cardiac Progenitor Cells and the Interplay with Their Microenvironment

Abstract

The microenvironment plays a crucial role in the behavior of stem and progenitor cells. In the heart, cardiac progenitor cells (CPCs) reside in specific niches, characterized by key components that are altered in response to a myocardial infarction. To date, there is a lack of knowledge on these niches and on the CPC interplay with the niche components. Insight into these complex interactions and into the influence of microenvironmental factors on CPCs can be used to promote the regenerative potential of these cells. In this review, we discuss cardiac resident progenitor cells and their regenerative potential and provide an overview of the interactions of CPCs with the key elements of their niche. We focus on the interaction between CPCs and supporting cells, extracellular matrix, mechanical stimuli, and soluble factors. Finally, we describe novel approaches to modulate the CPC niche that can represent the next step in recreating an optimal CPC microenvironment and thereby improve their regeneration capacity.

Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials

“…This could mean that the microenvironment of the heart might have a key role in CPC functions. Stem and progenitor cells reside in specific tissue microenvironments, called niches, which provide protection and support to the cells [241]. A way to potentially enhance CPC regenerative potential could be to mimic their microenvironment.…”

Development of the Myocardial Interstitium

“…Cardiac interstitial cells include endothelial and smooth muscle cells, pericytes, peripheral nerves and a number of resident mesenchymal cell populations, including cardiac fibroblasts (CF) (Ruiz‐Villalba et al, ; Pinto et al, ) and cardiac resident stem cells (Beltrami et al, ; Urbanek et al, ; Mauretti et al, ). The identification of this latter group of cells, which was primarily as based on the cellular expression of molecules like Sca‐1, c‐Kit, or Isl‐1 (Martin‐Puig et al, , Anversa et al, ), has promoted the idea that cardiovascular progenitor/stem cells (CSC) are the primary agents responsible for cardiomyocyte homeostatic renewal (Beltrami et al, ; Leri et al, ).…”

“…The CI is frequently referred‐to as “the cardiac niche” (Mauretti et al, ). This interpretation of the cardiac interstitial milieu as a particular form of microenvironment is bound to the early description of CSCs (Urbanek et al, ).…”

Cardiac Progenitor Cells: The Matrix Has You

“…Specifically, components of cardiac ECM are synthesized by residing cells, like fibroblasts, cardiac myocytes, and endothelial cells , and are continuously remodeled by the same cells according to ever‐changing conditions. Nonetheless, residing cells (including primitive cells) receive constant biochemical and mechanical signals from the ECM that affect cell survival, proliferation, migration, and differentiation .…”

“…These concepts highlight the importance of a multifactorial perspective on cardiac regenerative medicine (Fig. ), where the crosstalk between the host microenvironment and regenerative cell type(s) determines indeed the therapeutic outcome . It is of great importance to create and sustain microenvironment conditions that favor cardiogenic commitment of therapeutic cells and minimize pro‐fibrotic or inflammatory signals, while conversely boosting the capacity of therapeutic cells to promote tissue protection and counteract adverse remodeling of the ECM.…”