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README.md

License: CC BY 4.0 GitHub issue last update

Mechanically Induced Development and Maturation of Human Intestinal Organoids in Vivo

Holly M. Poling1, David Wu2, Nicole Brown1, Michael Baker3, Taylor A. Horras1, Nhan Huynh4+, Samuel Chaffron5, James C.Y. Dunn4+,6, Simon P. Hogan2, James M. Wells7,8, Michael A. Helmrath1 and Maxime M. Mahe1,9*

1 Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 USA; 2 Department of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 USA; 3 Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03766 USA; 4 Department of Bioengineering, Department of Surgery, University of California, Los Angeles, Los Angeles, CA 90095 USA; 5 UMR 6004 CNRS, University of Nantes, 2 Chemin de la Houssinière, 44322 Nantes Cedex 1, France 6 Department of Surgery - Pediatric Surgery, Department of Bioengineering, Stanford University, 300 Pasteur Drive, Always M116, Stanford, CA 94305 USA; 7 Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229 USA; 8 Division of Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 USA; 9 Inserm 1235 Unit, University of Nantes, 1 Rue Gaston Veil, 44035 Nantes Cedex 1, France; + previous affiliation

*Corresponding Author: maxime.mahe@inserm.fr


Summary

In both directing and fostering the natural ability of stem cells to self-organize, significant advances have been made in the generation of functional human intestinal organoids. However, conventional methods for their generation are solely biological, when indeed intestinal development and morphogenesis are impacted by dynamic mechanical forces. As our understanding of these mechanical forces during development deepens, we are presented with the opportunity to include them in our tissue engineering strategies. Here we have taken an interdisciplinary approach to the generation of intestinal tissue and incorporated uniaxial strain serving to induce growth and maturation of the tissue. Using a variety of outcome measures including morphometric quantification, transcriptome profiling, and functional assays, we found the newly generated tissue to be more similar to native human intestine after strain exposure. The size and complexity of the tissue was significantly improved as was muscle tone. This novel methodology incorporates a developmentally relevant mechanical cue in the development of human intestinal tissue and results in enhanced maturation and enterogenesis.


Outline

This repository contains the following sections :


About this repository

This repository contains datasets and R scripts related to the manuscript "Mechanically Induced Development and Maturation of Human Intestinal Organoids in Vivo". This repository will continue to undergo changes unless noted in this README.

The accession number for data generated for this paper is ArrayExpress: E-MTAB-6017 and includes the transplanted HIO, with or without lengthening device, the human adult and infant data .

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