Journal
NATURE BIOMEDICAL ENGINEERING
Volume 2, Issue 6, Pages 429-442Publisher
NATURE RESEARCH
DOI: 10.1038/s41551-018-0243-9
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Funding
- NIH [P30 DK078392]
- NIH NIDKK grant [1K99DK110414-02]
- Athena Blackburn Research Scholar Award in neuroenteric diseases from American Gastroenterology Association
- 'New Team' grant from Bioregate Regenerative Medicine Cluster, University of Nantes
- Pays de la Loire Region
- NIDDK
- NIAID [U01DK103117]
- Cincinnati Children's Research Foundation
- Cincinnati Biobank
- Better Outcomes for Children Biorepository
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [U18EB021780] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K99DK110414, U01DK103117, P30DK078392] Funding Source: NIH RePORTER
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The natural ability of stem cells to self-organize into functional tissue has been harnessed for the production of functional human intestinal organoids. Although dynamic mechanical forces play a central role in intestinal development and morphogenesis, conventional methods for the generation of intestinal organoids have relied solely on biological factors. Here, we show that the incorporation of uniaxial strain, using compressed nitinol springs, in human intestinal organoids transplanted into the mesentery of mice induces growth and maturation of the organoids. Assessment of morphometric parameters, transcriptome profiling and functional assays of the strain-exposed tissue revealed higher similarities to native human intestine, with regard to tissue size and complexity, and muscle tone. Our findings suggest that the incorporation of physiologically relevant mechanical cues during the development of human intestinal tissue enhances its maturation and enterogenesis.
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