Figure 1
From: Topological and electrical control of cardiac differentiation and assembly
Engineering heart tissue for replacement therapeutics and in vitro models by physical and electrical control of cells and microenvironment. Depiction of current methods used to manipulate heart cells to develop, mature, and assemble into functional heart tissue. Tuning the cell microenvironment by means of geometry and electrical control exhibits upstream effects on adhesion, cell-cell and cell-extracellular matrix interactions, growth and differentiation, cellular and tissue alignment via cytoskeletal organization, and electrical and contractile apparatus. The small dark arrows in the flow diagrams indicate the sequence by which the specific method of microenvironmental control effectively manifests downstream. These end changes in the cardiac cells include changes in gene/protein expression, electrical properties, and mechanical properties. Top: during development pluripotent stem cells differentiate into mesodermal progenitors, then cardiovascular progenitors that give rise to various cell types in the heart (cardiomyocytes, fibroblasts, endothelial and smooth muscle cells). Cell differentiation and assembly into a highly organized structure is governed by biochemical, mechanical and electrical stimuli in vivo. Tissue engineering aims to recapitulate some of these environmental factors in vitro. Middle: control of substrate topography and stiffness affects cell orientation and, as a result, functional properties. Bottom: control of electrical properties is achieved by use of conductive biomaterials, electrical stimulation bioreactors or changes in gene expression of key ion channels. The large green arrows (middle and bottom) depict the span of current techniques used in the field and link them to the regimes of cardiac differentiation and assembly where they have been applied (top). CM, cardiomyocyte; CVP, cardiovascular progenitor; E-C, excitation-contraction; EC, endothelial cell; ECM, extracellular matrix; ET, excitation threshold; FB, fibroblast; MCR, maximum capture rate; PSC, pluripotent stem cell; SMC, smooth muscle cell.