Engineered In Vitro Disease Models

Abstract

The ultimate goal of most biomedical research is to gain greater insight into mechanisms of human disease or to develop new and improved therapies or diagnostics. Although great advances have been made in terms of developing disease models in animals, such as transgenic mice, many of these models fail to faithfully recapitulate the human condition. In addition, it is difficult to identify critical cellular and molecular contributors to disease or to vary them independently in whole-animal models. This challenge has attracted the interest of engineers, who have begun to collaborate with biologists to leverage recent advances in tissue engineering and microfabrication to develop novel in vitro models of disease. As these models are synthetic systems, specific molecular factors and individual cell types, including parenchymal cells, vascular cells, and immune cells, can be varied independently while simultaneously measuring system-level responses in real time. In this article, we provide some examples of these efforts, including engineered models of diseases of the heart, lung, intestine, liver, kidney, cartilage, skin and vascular, endocrine, musculoskeletal, and nervous systems, as well as models of infectious diseases and cancer. We also describe how engineered in vitro models can be combined with human inducible pluripotent stem cells to enable new insights into a broad variety of disease mechanisms, as well as provide a test bed for screening new therapies.

Fluidic Culture and Analysis of Pulmonary Artery Smooth Muscle Cells for the Study of Pulmonary Hypertension

“…Recently, microfluidic cell culture systems have been developed to sustain functionality of living organs. [8][9][10][11] In the area of vascular research, there are reports of vascular endothelial cell culture within a microchannel 12,13 and binding of leucocytes and endothelial cells.…”

Systems biology for organotypic cell cultures

“…The loss of these mechanical and spatial cues in culture alters the physiology and function of cells (Huh et al, 2012a). To address these limitations, more physiologically complex and relevant cell culture formats have been produced through biomedical engineering applications and are variously referred to as "organotypic", "organoid", or, when microfabrication techniques are used, "organ-on-a-chip" or "microfluidic" cell culture systems (Benam et al, 2015;Huh et al, 2012b). These engineered cell culture systems supported by advances in human-derived stem cells, aim at developing new tools for broad applications in preclinical drug testing and toxicant screening, and have been supported by substantial funding initiatives.…”

Endosteal-like extracellular matrix expression on melt electrospun written scaffolds

“…The crosstalk between cells and their microenvironment can be investigated if these processes are broken-down and systematically analysed using a versatile technology platform that incorporates tissue-specific extracellular matrix (ECM) elements [1]. Tissue engineering has produced advanced tools that integrate cells into scaffolds and matrices that mimic specific features and the 3-dimensionality (3D) of their natural niche [2].…”