Introduction to special issue

Approximating organs

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Science  07 Jun 2019:
Vol. 364, Issue 6444, pp. 946-947
DOI: 10.1126/science.aay1351

Lung-on-a-chip. The red and blue chambers are where airway cells are cultured to model human small airways. The device has six chambers for the generation of six biological replicates.

PHOTO: THE BIOLINES LABORATORY DIRECTED BY D. HUH AT THE UNIVERSITY OF PENNSYLVANIA

Less complex than a whole organ but more representative than clusters of cells in culture, organoids are composed of specific cell types that self-organize and recapitulate various aspects of organogenesis. As such, these 3D models enable studies of early organ development and tissue interactions. Furthermore, when constructed from patient-derived cells, they help us understand what happens in the disease state, including cancer. However, organs in a dish only approximate the real thing. They lack elements of the natural environment that are critical for influencing cell dynamics and morphogenesis. In addition, multiple cell lineages may contribute to a single organ, or physical features may be key. Hence, researchers are tasked with identifying and reconstructing these elements and interactions—whether they involve coculture with other cells to generate vasculature and provide innervation, or simulation of fluid flow as with organoids-on-a-chip. These engineered biological constructs can then more closely approximate nature's form and function. Continued tweaking of methods will yield exciting advances and solve classical embryology questions surrounding the generation of the three germ layers, breaking of symmetry, and axis formation, and may eventually lead to the replacement of faulty body parts though transplantation of organoid-generated tissues and organs.

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