Dataset Information

In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses.

ABSTRACT: There is a need for functional in vitro 3D human intestine systems that can bridge the gap between conventional cell culture studies and human trials. The successful engineering in vitro of human intestinal tissues relies on the use of the appropriate cell sources, biomimetic scaffolds, and 3D culture conditions to support vital organ functions. We previously established a compartmentalized scaffold consisting of a hollow space within a porous bulk matrix, in which a functional and physiologically relevant intestinal epithelium system was generated using intestinal cell lines. In this study, we adopt the 3D scaffold system for the cultivation of stem cell-derived human small intestinal enteriods (HIEs) to engineer an in vitro 3D model of a nonstransformed human small intestinal epithelium. Characterization of tissue properties revealed a mature HIE-derived epithelium displaying four major terminally differentiated epithelial cell types (enterocytes, Goblet cells, Paneth cells, enteroendocrine cells), with tight junction formation, microvilli polarization, digestive enzyme secretion, and low oxygen tension in the lumen. Moreover, the tissue model demonstrates significant antibacterial responses to E. coli infection, as evidenced by the significant upregulation of genes involved in the innate immune response. Importantly, many of these genes are activated in human patients with inflammatory bowel disease (IBD), implicating the potential application of the 3D stem-cell derived epithelium for the in vitro study of host-microbe-pathogen interplay and IBD pathogenesis.

SUBMITTER: Chen Y

PROVIDER: S-EPMC5706668 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses.

Chen Ying Y Zhou Wenda W Roh Terrence T Estes Mary K MK Kaplan David L DL

PloS one 20171129 11

There is a need for functional in vitro 3D human intestine systems that can bridge the gap between conventional cell culture studies and human trials. The successful engineering in vitro of human intestinal tissues relies on the use of the appropriate cell sources, biomimetic scaffolds, and 3D culture conditions to support vital organ functions. We previously established a compartmentalized scaffold consisting of a hollow space within a porous bulk matrix, in which a functional and physiological ...[more]

PMID: 29186150

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Project description:Three-dimensional (3D) in vitro tissue models are superior to two-dimensional (2D) cell cultures in replicating natural physiological/pathological conditions by recreating the cellular and cell-matrix interactions more faithfully. Nevertheless, current 3D models lack either the rich multicellular environment or fail to provide appropriate biophysical stimuli both of which are required to properly recapitulate the dynamic in vivo microenvironment of tissues and organs. Here, we describe the rapid construction of multicellular, tubular tissue constructs termed Tissue-in-a-Tube using self-assembly process in tubular molds with the ability to incorporate a variety of biophysical stimuli such as electrical field, mechanical deformation, and shear force of the fluid flow. Unlike other approaches, this method is simple, requires only oxygen permeable silicone tubing that molds the tissue construct and thin stainless-steel pins inserted in it to anchor the construct and could be used to provide electrical and mechanical stimuli, simultaneously. The annular region between the tissue construct and the tubing is used for perfusion. Highly stable, macroscale, and robust constructs anchored to the pins form as a result of self-assembly of the extracellular matrix (ECM) and cells in the bioink that is filled into the tubing. We demonstrate patterning of grafts containing cell types in the constructs in axial and radial modes with clear interface and continuity between the layers. Different environmental factors affecting cell behavior such as compactness of the structure and size of the constructs can be controlled through parameters such as initial cell density, ECM content, tubing size, as well as the distance between anchor pins. Using connectors, network of tubing can be assembled to create complex macrostructured tissues (centimeters length) such as fibers that are bifurcated or columns with different axial thicknesses which can then be used as building blocks for biomimetic constructs or tissue regeneration. The method is versatile and compatible with various cell types including endothelial, epithelial, skeletal muscle cells, osteoblast cells, and neuronal cells. As an example, long mature skeletal muscle and neuronal fibers as well as bone constructs were fabricated with cellular alignment dictated by the applied electrical field. The versatility, speed, and low cost of this method is suited for widespread application in tissue engineering and regenerative medicine.

Dataset Information

In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses.

Publications

In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses.

Similar Datasets

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