Human cardiac extracellular matrix supports myocardial lineage commitment of pluripotent stem cells†

Abstract

Human cardiac ECM seems to direct differentiation of pluripotent stem cells towards a cardiomyocyte phenotype. This phenomenon supports the use of cardiac ECM preparations for guided stem cell differentiation and myocardial repair, and may ultimately increase the therapeutic efficacy of cell therapy in heart failure patients.

Fibroblast-Derived Extracellular Matrix Induces Chondrogenic Differentiation in Human Adipose-Derived Mesenchymal Stromal/Stem Cells in Vitro

“…The ECM regulates the function of cells and drives cellular differentiation. Thus ECMs show bioactivities including inducing proliferation and differentiation [2,5,8,9]. The in vitro bioactivities of many synthetic and natural ECMs are not fully understood.…”

“…One of the greatest challenges in utilizing stem cells for tissue repair is directing gene regulation and guiding stem cell differentiation toward a specific lineage [1,4,9,10,12,13,14]. Mesenchymal stromal/stem cells (MSCs) have been shown to be able to proliferate considerably and can differentiate into various tissue lineages when induced.…”

Cardiac Extracellular Matrix Scaffold Generated Using Sarcomeric Disassembly and Antigen Removal

“…5 However, with only a few exceptions, most groups continue using denaturing detergents, such as sodium dodecyl sulfate (SDS), as their main active agent. 16,20,21,27,28 Reliance on potentially harsh detergents to achieve decellularization of cECM may in large part be due to challenges involved in achieving solubilization of the complex macromolecular components of the cardiac sarcomere. Unfortunately, although effective in removing cellular elements, some detergents have been associated with irreversible alterations of crucial cECM components that could negatively impact scaffold mechanical properties and inhibit downstream recellularization efforts and/or the in vivo remodeling response.…”

Materials for cardiac tissue engineering

“…In vitro studies using myocardial ECM as a scaffold demonstrate cell engraftment and differentiation towards cardiac [109,[112][113][114][115] and endothelial lineage [113][114][115], beside spontaneous recellularised scaffold contraction [112,114]. These promising findings may promote in vivo testing of cell reseeded decellularised myocardial ECM scaffolds for MI repair.…”

“…In vitro studies demonstrate that pericardial-derived ECM allows cell survival, growth and attachment induced pluripotent stem cells (iPSCs)-derived cardiomyocytes and MSCs [109], and also facilitates differentiation of progenitor cells derived from adipose [110] and cardiac [108] tissue towards endothelial or cardiac cell lineage, respectively. Furthermore, decellularised human pericardium embedded with self-assembling peptide RAD16-I and adipose tissue--derived progenitor cells (ATDPCs) increases scaffold vascularisation and reduces infarct size one month after implantation in the swine MI model ( Figure 2 E-G) [110].…”