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Stem Cell Reports. 2019 Feb 12;12(2):381-394. doi: 10.1016/j.stemcr.2018.12.001. Epub 2019 Jan 3.

Nonadhesive Alginate Hydrogels Support Growth of Pluripotent Stem Cell-Derived Intestinal Organoids.

Author information

1
Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI 48109, USA.
2
Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
3
Division of Pediatric General and Thoracic Surgery Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
4
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory School of Medicine, Atlanta, GA 30332, USA.
5
Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
6
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
7
Division of Pediatric General and Thoracic Surgery Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM) Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.
8
Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Center for Organogenesis, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: spencejr@umich.edu.

Abstract

Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. In addition, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.

KEYWORDS:

alginate; enteroid; human pluripotent stem cell; hydrogel; intestinal organoid; intestine; organoid

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