title: 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.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115; email: don.ingber@wyss.harvard.edu.
authors.forename: Kambez H
authors.initials: KH
authors.lastname: Benam
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dauth
authors.forename: Bryan
authors.initials: B
authors.lastname: Hassell
authors.forename: Anna
authors.initials: A
authors.lastname: Herland
authors.forename: Abhishek
authors.initials: A
authors.lastname: Jain
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Jang
authors.forename: Katia
authors.initials: K
authors.lastname: Karalis
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Luke
authors.initials: L
authors.lastname: MacQueen
authors.forename: Roza
authors.initials: R
authors.lastname: Mahmoodian
authors.forename: Samira
authors.initials: S
authors.lastname: Musah
authors.forename: Yu-suke
authors.initials: YS
authors.lastname: Torisawa
authors.forename: Andries D
authors.initials: AD
authors.lastname: van der Meer
authors.forename: Remi
authors.initials: R
authors.lastname: Villenave
authors.forename: Moran
authors.initials: M
authors.lastname: Yadid
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Parker
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D000818:Animals; D004194:Disease; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010336:Pathology / Q000379:methods*
keywords: 3D culture; disease model; in vitro tool; microfluidic; organ-on-a-chip; tissue engineering