Programming Cellular Alignment in Engineered Cardiac Tissue via Bioprinting Anisotropic Organ Building Blocks.

The ability to replicate the 3D myocardial architecture found in human hearts is a grand challenge. Here, the fabrication of aligned cardiac tissues via bioprinting anisotropic organ building blocks (aOBBs) composed of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is reported. A bioink composed of contractile cardiac aOBBs is first generated and aligned cardiac tissue sheets with linear, spiral, and chevron features are printed.

Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels.

Engineering organ-specific tissues for therapeutic applications is a grand challenge, requiring the fabrication and maintenance of densely cellular constructs composed of ~10 cells/ml. Organ building blocks (OBBs) composed of patient-specific-induced pluripotent stem cell-derived organoids offer a pathway to achieving tissues with the requisite cellular density, microarchitecture, and function. However, to date, scant attention has been devoted to their assembly into 3D tissue constructs.

Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro.

Understanding individual susceptibility to drug-induced cardiotoxicity is key to improving patient safety and preventing drug attrition. Human induced pluripotent stem cells (hiPSCs) enable the study of pharmacological and toxicological responses in patient-specific cardiomyocytes (CMs) and may serve as preclinical platforms for precision medicine. Transcriptome profiling in hiPSC-CMs from seven individuals lacking known cardiovascular disease-associated mutations and in three isogenic human heart tissue and hiPSC-CM pairs showed greater inter-patient variation than intra-patient variation, verifying that reprogramming and differentiation preserve patient-specific gene expression, particularly in metabolic and stress-response genes.

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

Human induced pluripotent stem cells (hiPSCs) have revolutionized the field of human disease modeling, with an enormous potential to serve as paradigm shifting platforms for preclinical trials, personalized clinical diagnosis, and drug treatment. In this review, we describe how hiPSCs could transition cardiac healthcare away from simple disease diagnosis to prediction and prevention, bridging the gap between basic and clinical research to bring the best science to every patient.