New Maintenance Culture Method for Intestinal Stem Cells Derived from Human Induced Pluripotent Stem Cells

Most orally administered drugs exert their effects after being absorbed in the small intestine. Therefore, new drugs must undergo nonclinical pharmacokinetic evaluations in the small intestine. Enterocytes derived from human induced pluripotent stem cells (hiPSCs) are expected to be used in the eval...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2024/01/01, Vol.47(1), pp.120-129
Main Authors: Mizuno, Shota, Jinnoh, Yumi, Arita, Ayaka, Qiu, Shimeng, Hashita, Tadahiro, Hori, Eisei, Iwao, Takahiro, Matsunaga, Tamihide
Format: Article
Language:English
Subjects:
Acetylcysteine
Cell culture
Cell differentiation
drug development
enterocyte
Enterocytes
Fibroblast growth factor 2
Growth factors
human induced pluripotent stem cell
intestinal stem cell
maintenance culture
Nicotinamide
Noggin protein
Oral administration
Organoids
Pharmacokinetics
Pluripotency
Small intestine
Stem cells
Valproic acid
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Summary:Most orally administered drugs exert their effects after being absorbed in the small intestine. Therefore, new drugs must undergo nonclinical pharmacokinetic evaluations in the small intestine. Enterocytes derived from human induced pluripotent stem cells (hiPSCs) are expected to be used in the evaluation system, as they reflect human intestinal characteristics more accurately; moreover, several differentiation protocols are available for these cells. However, enterocytes derived from hiPSCs have drawbacks such as time, cost, and lot-to-lot differences. Hence, to address these issues, we attempted to maintain hiPSC-derived intestinal stem cells (ISCs) that can differentiate into various intestinal cells by regulating various pathways. Although our previous attempt was partly successful, the drawbacks of elevated cost and complicated handling remained, because more than 10 factors (A 83-01, CHIR99021, epidermal growth factor, basic fibroblast growth factor, SB202190, nicotinamide, N-acetylcysteine, valproic acid, Wnt3a, R-spondin 1, and noggin) are needed to maintain ISCs. Therefore, in this study, we successfully maintained ISCs using only five factors, including growth factors. Moreover, we generated not only enterocytes but also intestinal organoids from the maintained ISCs. Thus, our novel findings provided a time-saving and cost-effective culture method for enterocytes derived from hiPSCs.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b23-00573