Geometric engineering of organoid culture for enhanced organogenesis in a dish.

Autor: Park SE; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; NSF Science and Technology Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA, USA., Kang S; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Paek J; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Georgescu A; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; Vivodyne, Inc., Philadelphia, PA, USA., Chang J; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.; NSF Science and Technology Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA, USA., Yi AY; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA., Wilkins BJ; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Karakasheva TA; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Hamilton KE; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Huh DD; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. huhd@seas.upenn.edu.; NSF Science and Technology Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA, USA. huhd@seas.upenn.edu.; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. huhd@seas.upenn.edu.
Jazyk: angličtina
Zdroj: Nature methods [Nat Methods] 2022 Nov; Vol. 19 (11), pp. 1449-1460. Date of Electronic Publication: 2022 Oct 24.
DOI: 10.1038/s41592-022-01643-8
Abstrakt: Here, we introduce a facile, scalable engineering approach to enable long-term development and maturation of organoids. We have redesigned the configuration of conventional organoid culture to develop a platform that converts single injections of stem cell suspensions to radial arrays of organoids that can be maintained for extended periods without the need for passaging. Using this system, we demonstrate accelerated production of intestinal organoids with significantly enhanced structural and functional maturity, and their continuous development for over 4 weeks. Furthermore, we present a patient-derived organoid model of inflammatory bowel disease (IBD) and its interrogation using single-cell RNA sequencing to demonstrate its ability to reproduce key pathological features of IBD. Finally, we describe the extension of our approach to engineer vascularized, perfusable human enteroids, which can be used to model innate immune responses in IBD. This work provides an immediately deployable platform technology toward engineering more realistic organ-like structures in a dish.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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