A 96-well format microvascularized human lung-on-a-chip platform for microphysiological modeling of fibrotic diseases

Author(s): Joscelyn C. Mejías ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Michael R. Nelson ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Olivia Liseth ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Krishnendu Roy ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵

Publication date (Electronic): 2020

Journal: Lab on a Chip

Publisher: Royal Society of Chemistry (RSC)

Read this article at

ScienceOpenPublisher PubMed

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

A 3D microvascularized lung-on-a-chip device for modeling pulmonary diseases.

Abstract

Development of organoids and microfluidic on-chip models has enabled studies of organ-level disease pathophysiologies in vitro. However, current lung-on-a-chip platforms are primarily monolayer epithelial–endothelial co-cultures, separated by a thin membrane, lacking microvasculature-networks or interstitial-fibroblasts. Here we report the design, microfabrication, and characterization of a unique microphysiological on-chip device that recapitulates the human lung interstitium–airway interface through a 3D vascular network, and normal or diseased fibroblasts encapsulated within a fibrin-collagen hydrogel underneath an airlifted airway epithelium. By incorporating fibroblasts from donors with idiopathic pulmonary fibrosis (IPF), or healthy-donor fibroblasts treated with TGF-β1, we successfully created a fibrotic, alpha smooth muscle actin (αSMA)-positive disease phenotype which led to fibrosis-like transformation in club cells and ciliated cells in the airway. Using this device platform, we further modeled the cystic fibrosis (CF) epithelium and recruitment of neutrophils to the vascular networks. Our results suggest that this microphysiological model of the human lung could enable more pathophysiologically relevant studies of complex pulmonary diseases.

Related collections

Most cited references 1

Record: found
Abstract: found
Article: not found

A Multi-Niche Microvascularized Human Bone-Marrow-on-a-Chip

Michael R. Nelson, Delta Ghoshal, Joscelyn C. Mejías … (2019)

The human bone marrow (hBM) is a complex organ critical for hematopoietic and immune homeostasis, and where many cancers metastasize. Yet, understanding the fundamental biology of the hBM in health and diseases remain difficult due to complexity of studying or manipulating the BM in humans. Accurate in vitro models of the hBM microenvironment are critical to further our understanding of the BM niche and advancing new clinical interventions. Although, in vitro culture models that recapitulate some key components of the BM niche have been reported, there are no examples of a fully human, in vitro , organoid platform that incorporates the various niches of the hBM - specifically the endosteal, central marrow, and perivascular niches – thus limiting their physiological relevance. Here we report an hBM-on-a-chip that incorporates these three niches in a single micro-physiological device. Osteogenic differentiation of hMSCs produced robust mineralization on the PDMS surface (“bone layer”) and subsequent seeding of endothelial cells and hMSCs in a hydrogel network (“central marrow”) created an interconnected vascular network (“perivascular niche”) on top. We show that this multi-niche hBM accurately mimics the ECM composition, allows hematopoietic progenitor cell proliferation and migration, and is affected by radiation. A key finding is that the endosteal niche significantly contributes to hBM physiology. Taken together, this multi-niche micro-physiological system opens up new opportunities in hBM research and therapeutics development, and can be used to better understand hBM physiology, normal and impaired hematopoiesis, and hBM pathologies, including cancer metastasis, multiple myelomas, and BM failures.