New Model for Lung Disease Research Based on Stem Cell-derived Lung Organoids

By manipulating cocktails of growth factors, researchers have stimulated human stem cells to morph into tissues that self-organize into three-dimensional structures populated by cells resembling those in the lung.

The research leading to development of these lung organoids was based on recent breakthroughs in three-dimensional organoid cultures for many organ systems, which have led to new physiologically complex in vitro models to study human development and disease.

In the current study, investigators at the University of Michigan (Ann Arbor, USA) manipulated developmental signaling pathways to guide the step-wise differentiation of human pluripotent stem cells (hPSCs) (embryonic and induced) into lung organoids.

They reported in the March 24, 2015, online edition of the journal eLife that hPSCs generated ventral-anterior foregut spheroids, which were then expanded into human lung organoids (HLOs). HLOs consisted of epithelial and mesenchymal compartments of the lung, organized with structural features similar to the native lung. HLOs possessed upper airway-like epithelium with basal cells and immature ciliated cells surrounded by smooth muscle and myofibroblasts as well as an alveolar-like domain with appropriate cell types. HLOs were able to survive in culture for more than 100 days.

Using RNA-sequencing, the investigators showed that HLOs were remarkably similar to human fetal lung based on global transcriptional profiles, suggesting that HLOs would be an excellent model system for the study of human lung development, maturation, and disease.

“These mini lungs can mimic the responses of real tissues and will be a good model to study how organs form, change with disease, and how they might respond to new drugs,” said senior author Dr. Jason R. Spence, assistant professor of internal medicine and cell and developmental biology at the University of Michigan.

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