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用于源自人肠道类器官的肠道干细胞的化学成分明确且可扩展的培养系统。

Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids.

作者信息

Kwon Ohman, Lee Hana, Jung Jaeeun, Son Ye Seul, Jeon Sojeong, Yoo Won Dong, Son Naeun, Jung Kwang Bo, Choi Eunho, Lee In-Chul, Kwon Hyung-Jun, Kim Chuna, Lee Mi-Ok, Cho Hyun-Soo, Kim Dae Soo, Son Mi-Young

机构信息

Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.

KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea.

出版信息

Nat Commun. 2024 Jan 27;15(1):799. doi: 10.1038/s41467-024-45103-7.

DOI:10.1038/s41467-024-45103-7
PMID:38280855
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10821882/
Abstract

Three-dimensional human intestinal organoids (hIO) are widely used as a platform for biological and biomedical research. However, reproducibility and challenges for large-scale expansion limit their applicability. Here, we establish a human intestinal stem cell (ISC) culture method expanded under feeder-free and fully defined conditions through selective enrichment of ISC populations (ISC) within hIO derived from human pluripotent stem cells. The intrinsic self-organisation property of ISC, combined with air-liquid interface culture in a minimally defined medium, forces ISC to differentiate into the intestinal epithelium with cellular diversity, villus-like structure, and barrier integrity. Notably, ISC is an ideal cell source for gene editing to study ISC biology and transplantation for intestinal diseases. We demonstrate the intestinal epithelium differentiated from ISC as a model system to study severe acute respiratory syndrome coronavirus 2 viral infection. ISC culture technology provides a biological tool for use in regenerative medicine and disease modelling.

摘要

三维人类肠道类器官（hIO）被广泛用作生物学和生物医学研究的平台。然而，可重复性以及大规模扩增面临的挑战限制了它们的适用性。在此，我们建立了一种人类肠道干细胞（ISC）培养方法，该方法通过在源自人类多能干细胞的hIO内选择性富集ISC群体，在无饲养层且完全确定的条件下进行扩增。ISC固有的自我组织特性，与在最低限度定义的培养基中进行气液界面培养相结合，促使ISC分化为具有细胞多样性、绒毛样结构和屏障完整性的肠上皮。值得注意的是，ISC是用于基因编辑以研究ISC生物学以及用于肠道疾病移植的理想细胞来源。我们证明了从ISC分化而来的肠上皮可作为研究严重急性呼吸综合征冠状病毒2病毒感染的模型系统。ISC培养技术为再生医学和疾病建模提供了一种生物学工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/82410a0ae629/41467_2024_45103_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/179e2d245d91/41467_2024_45103_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/64a127c2bb43/41467_2024_45103_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/fed581ef051c/41467_2024_45103_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/e4bdc402a5eb/41467_2024_45103_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/c15f66abe72c/41467_2024_45103_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/bff29731a1ca/41467_2024_45103_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/82410a0ae629/41467_2024_45103_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/179e2d245d91/41467_2024_45103_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/64a127c2bb43/41467_2024_45103_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/fed581ef051c/41467_2024_45103_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/e4bdc402a5eb/41467_2024_45103_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/c15f66abe72c/41467_2024_45103_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/bff29731a1ca/41467_2024_45103_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f40d/10821882/82410a0ae629/41467_2024_45103_Fig7_HTML.jpg

相似文献

[1]
Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids.

Nat Commun. 2024-1-27

[2]
The Lumen of Human Intestinal Organoids Poses Greater Stress to Bacteria Compared to the Germ-Free Mouse Intestine: Escherichia coli Deficient in RpoS as a Colonization Probe.

mSphere. 2020-11-11

[3]
Effects of human induced pluripotent stem cell-derived intestinal organoids on colitis-model mice.

Regen Ther. 2022-9-9

[4]
Transplanted human intestinal organoids: a resource for modeling human intestinal development.

Development. 2023-5-1

[5]
Generation of Highly Expandable Intestinal Spheroids Composed of Stem Cells.

Int J Stem Cells. 2022-2-28

[6]
Nonadhesive Alginate Hydrogels Support Growth of Pluripotent Stem Cell-Derived Intestinal Organoids.

Stem Cell Reports. 2019-1-3

[7]
Suspension culture of human induced pluripotent stem cell-derived intestinal organoids using natural polysaccharides.

Biomaterials. 2022-9

[8]
Advancing Intestinal Organoid Technology Toward Regenerative Medicine.

Cell Mol Gastroenterol Hepatol. 2017-11-2

[9]
Differentiation of Human Intestinal Organoids with Endogenous Vascular Endothelial Cells.

Dev Cell. 2020-8-24

[10]
In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice.

Nat Biotechnol. 2023-6

引用本文的文献

[1]
Biomedical applications of organoids derived from the digestive system.

Front Cell Dev Biol. 2025-5-30

[2]
Biomimetic culture substrates for modelling homeostatic intestinal epithelium in vitro.

Nat Commun. 2025-5-3

[3]
Xenogeneic-free culture of human intestinal stem cells on functional polymer-coated substrates for scalable, clinical-grade stem cell therapy.

Nat Commun. 2024-12-2

本文引用的文献

[1]
Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions.

Commun Biol. 2023-4-8

[2]
ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology.

Front Mol Biosci. 2021-9-21

[3]
Cells of the human intestinal tract mapped across space and time.

Nature. 2021-9

[4]
Selinexor, a novel selective inhibitor of nuclear export, reduces SARS-CoV-2 infection and protects the respiratory system in vivo.

Antiviral Res. 2021-8

[5]
In vitro models of intestinal epithelium: Toward bioengineered systems.

J Tissue Eng. 2021-2-1

[6]
The development of a functional human small intestinal epithelium model for drug absorption.

Sci Adv. 2021-6

[7]
Charting human development using a multi-endodermal organ atlas and organoid models.

Cell. 2021-6-10

[8]
An organoid-based organ-repurposing approach to treat short bowel syndrome.

Nature. 2021-4

[9]
Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn's Disease.

Dev Cell. 2020-12-21

[10]
Intestinal Morphogenesis in Development, Regeneration, and Disease: The Potential Utility of Intestinal Organoids for Studying Compartmentalization of the Crypt-Villus Structure.

Front Cell Dev Biol. 2020-10-23

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