Bioengineering heart tissue for in vitro testing

Abstract

A classical paradigm of tissue engineering is to grow tissues for implantation by using human stem cells in conjunction with biomaterial scaffolds (templates for tissue formation) and bioreactors (culture systems providing environmental control). A reverse paradigm is now emerging through microphysiological platforms for preclinical testing of drugs and modeling of disease that contain large numbers of very small human tissues. We discuss the biomimetic approach as a common underlying principle and some of the specifics related to the design and utilization of platforms with heart micro-tissues for high-throughput screening in vitro.

Figure 1. In vitro platforms for studying physiological and pathological responses of engineered heart tissues

Studies of physiologic signals (top panel) include staged application of molecular regulatory factors (to induce differentiation of human iPS cells into cardiomoyocytes), the application of additional molecular factors, extracellular matrix and electromechanical factors to mature the cells and the use of the resulting tissues for drug screening. Studies of pathologic signals (bottom panel) involve the same steps as physiologic testing, except that the goal is modeling disease, by either using iPS cells from patients, or using factors (molecular, electrical, mechanical) causing specific pathological responses.