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

2019; Elsevier BV; Volume: 12; Issue: 2 Linguagem: Inglês

10.1016/j.stemcr.2018.12.001

2213-6711

Meghan M. Capeling, Michael Czerwinski, Sha Huang, Yu-Hwai Tsai, Angeline Wu, Melinda Nagy, Benjamin A. Juliar, Nambirajan Sundaram, Yang Song, Woojin M. Han, Shuichi Takayama, Eben Alsberg, Andrés J. Garcı́a, Michael A. Helmrath, Andrew J. Putnam, Jason R. Spence,

3D Printing in Biomedical Research

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.