Engineered heart tissues and induced pluripotent stem cells: Macro- and microstructures for disease modeling, drug screening, and translational studies

Abstract

Engineered heart tissue has emerged as a personalized platform for drug screening. With the advent of induced pluripotent stem cell (iPSC) technology, patient-specific stem cells can be developed and expanded into an indefinite source of cells. Subsequent developments in cardiovascular biology have led to efficient differentiation of cardiomyocytes, the force-producing cells of the heart. iPSC-derived cardiomyocytes (iPSC-CMs) have provided potentially limitless quantities of well-characterized, healthy, and disease-specific CMs, which in turn has enabled and driven the generation and scale-up of human physiological and disease-relevant engineered heart tissues. The combined technologies of engineered heart tissue and iPSC-CMs are being used to study diseases and to test drugs, and in the process, have advanced the field of cardiovascular tissue engineering into the field of precision medicine. In this review, we will discuss current developments in engineered heart tissue, including iPSC-CMs as a novel cell source. We examine new research directions that have improved the function of engineered heart tissue by using mechanical or electrical conditioning or the incorporation of non-cardiomyocyte stromal cells. Finally, we discuss how engineered heart tissue can evolve into a powerful tool for therapeutic drug testing.

Real-Time Force and Frequency Analysis of Engineered Human Heart Tissue Derived from Induced Pluripotent Stem Cells Using Magnetic Sensing

“…8,9,12,13 By studying hiPSC-CMs in engineered heart tissues, which are three-dimensional tissue constructs comprised of cardiomyocytes in a hydrogel, hiPSC-CMs show a more mature phenotype than two-dimensional cultured cardiomyocytes. [14][15][16][17][18][19] The three-dimensional environment recapitulates the cell-cell and cell-matrix interactions of the native myocardium, promoting hiPSC-CMs to have elongated shapes and a higher degree of myofibril organization.…”

Human Induced Pluripotent Stem Cells as a Platform for Personalized and Precision Cardiovascular Medicine

“…For the hiPSC technology, one major concern is the immature state of differentiated derivatives. This topic has been extensively discussed elsewhere (128,309), and several physical, chemical, and electrical signals are under investigation to enable these cells to mature to a state more closely resembling the adult human heart (124,208,266,276,309). Subtype specification of CMs (i.e., into pacemaker, atrial, or ventricular cells of either the right or left side of the heart) is also under investigation.…”

Multiscale technologies for treatment of ischemic cardiomyopathy

“…Although cell-based approaches to cardiac tissue engineering have made significant advances, a number of major challenges and limitations remain, including problems involving transplanted cell sources, viability and phenotype stability, as well as regulatory challenges 117 . Acellular biomaterials are evolving as alternatives to repair ischemic heart injury via delivery of therapeutics and/or stimulation of the native (endogenous) regenerative mechanisms 68 , along with basic physiomechanical support 118 .…”