Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids
To evaluate the intestinal absorption and metabolism of orally administered drugs, human induced pluripotent stem (iPS) cell‑derived enterocyte‑like cells (ELCs) are expected to be useful. In a previous report, we succeeded in developing a highly functional monolayer platform (ELC-org-mono) from hum...
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Elsevier
2025-06-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933525000044 |
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| author | Tatsuya Inui Yusei Uraya Yukiko Ueyama-Toba Hiroyuki Mizuguchi |
| author_facet | Tatsuya Inui Yusei Uraya Yukiko Ueyama-Toba Hiroyuki Mizuguchi |
| author_sort | Tatsuya Inui |
| collection | DOAJ |
| description | To evaluate the intestinal absorption and metabolism of orally administered drugs, human induced pluripotent stem (iPS) cell‑derived enterocyte‑like cells (ELCs) are expected to be useful. In a previous report, we succeeded in developing a highly functional monolayer platform (ELC-org-mono) from human iPS cell-derived ELCs through an organoid culture and demonstrated its suitability for pharmacokinetic studies. In recent years, the air–liquid interface (ALI) culture model was developed, allowing for the culture of epithelial tissue under conditions that mimic the in vivo environment. In the present study, we applied ALI culture to ELC-org-mono for further improvement of intestinal functions. ALI culture of ELC-org-mono greatly developed goblet cells and enhanced the gene expression levels of many drug-metabolizing enzymes, drug transporters and intestinal differentiation markers. However, their activities were not enhanced. RNA-seq analysis suggested that ALI culture increased the expression of genes related to metabolic processes but decreased glycolytic processes. Analysis of glycolytic capacity confirmed that ALI culture decreased glycolytic activities. Thus, there is room for some adjustment in the ALI culture model to optimize its applicability to pharmacokinetic studies using ELC-org-mono. |
| format | Article |
| id | doaj-art-5b7d5fdeb9ee43f7b44192e4f7444500 |
| institution | Kabale University |
| issn | 0171-9335 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj-art-5b7d5fdeb9ee43f7b44192e4f74445002025-02-08T04:59:27ZengElsevierEuropean Journal of Cell Biology0171-93352025-06-011042151479Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoidsTatsuya Inui0Yusei Uraya1Yukiko Ueyama-Toba2Hiroyuki Mizuguchi3Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Functional Organoid for Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka 565-0871, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Functional Organoid for Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka 565-0871, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Suita, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan; Correspondence to: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Osaka, Suita 565-0871, Japan.To evaluate the intestinal absorption and metabolism of orally administered drugs, human induced pluripotent stem (iPS) cell‑derived enterocyte‑like cells (ELCs) are expected to be useful. In a previous report, we succeeded in developing a highly functional monolayer platform (ELC-org-mono) from human iPS cell-derived ELCs through an organoid culture and demonstrated its suitability for pharmacokinetic studies. In recent years, the air–liquid interface (ALI) culture model was developed, allowing for the culture of epithelial tissue under conditions that mimic the in vivo environment. In the present study, we applied ALI culture to ELC-org-mono for further improvement of intestinal functions. ALI culture of ELC-org-mono greatly developed goblet cells and enhanced the gene expression levels of many drug-metabolizing enzymes, drug transporters and intestinal differentiation markers. However, their activities were not enhanced. RNA-seq analysis suggested that ALI culture increased the expression of genes related to metabolic processes but decreased glycolytic processes. Analysis of glycolytic capacity confirmed that ALI culture decreased glycolytic activities. Thus, there is room for some adjustment in the ALI culture model to optimize its applicability to pharmacokinetic studies using ELC-org-mono.http://www.sciencedirect.com/science/article/pii/S0171933525000044Intestinal organoidsSmall intestineIPS cellDrug-metabolizing enzymesDrug transporters |
| spellingShingle | Tatsuya Inui Yusei Uraya Yukiko Ueyama-Toba Hiroyuki Mizuguchi Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids European Journal of Cell Biology Intestinal organoids Small intestine IPS cell Drug-metabolizing enzymes Drug transporters |
| title | Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids |
| title_full | Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids |
| title_fullStr | Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids |
| title_full_unstemmed | Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids |
| title_short | Air-liquid interface culture alters the characteristics and functions of monolayers generated from human iPS cell‑derived enterocyte‑like cell organoids |
| title_sort | air liquid interface culture alters the characteristics and functions of monolayers generated from human ips cell derived enterocyte like cell organoids |
| topic | Intestinal organoids Small intestine IPS cell Drug-metabolizing enzymes Drug transporters |
| url | http://www.sciencedirect.com/science/article/pii/S0171933525000044 |
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