［Health Science domain］
Kirin and the University of Tokyo succeed in confirming the effectiveness of an anti-aging material using human iPS cell-derived small intestinal organoids for the first time in the world
- Research and Technology
March 11, 2025
Kirin Holdings Company, Limited
TOKYO, March 11, 2025 - Kirin Holdings Company, Limited (Kirin Holdings) and a research group led by Professor Ryuichiro Sato of the Graduate School of Agricultural and Life Sciences, The University of Tokyo have successfully confirmed for the first time in the world1 the efficacy of an anti-aging material in human induced pluripotent stem (iPS) cell-derived small intestinal organoids.2 In this study, we establish a cellular senescence model of small intestinal organoids using cisplatin,3 and confirmed the efficacy of human milk oligosaccharides (HMOs) in the model. The results of this research will be presented at the 2025 Annual Meeting of the Japan Society for Bioscience, Biotechnology, and Agrochemistry in Sapporo, Hokkaido, Japan, from March 4 (Tuesday) to March 8 (Saturday), 2025.
Research on “aging” is becoming increasingly important against the backdrop of a super-aging society. Kirin and the University of Tokyo started this research in 2022 on the theme of “intestinal aging,” which is one of the health issues in aging. Intestinal aging is difficult to assess in humans, and basic research and clarification of this issue have not made much progress, so various methods are being explored. We believe that the outcomes of this research, namely the successful establishment of a model of human iPS cell-derived small intestinal organoids that reproduce the characteristics of aging and confirmation of the efficacy of functional materials in this model, are significant as they constitute advanced examples of organoid utilization in the field of unwellness.
1 Based on an original article published in Medical Journal Web (survey conducted on February 20, 2025, by KnowledgeWire)
2 Organoids are three-dimensional structures that mimic organs and tissues, and are also called “artificial organs.”
3 An anticancer drug that exerts its anticancer effects by binding to biological components such as DNA.
Research results (summary)
(1) Using human iPS cell-derived small intestinal organoids, we have succeeded in establishing a model that recapitulates the hallmarks of aging, such as cellular senescence and the accompanying inflammatory response and loss of barrier function (Fig. 1).
(2) Using the model, we utilized and evaluated HMOs as a functional material known to inhibit intestinal inflammation and improve the barrier function, and confirmed significant improvement in the aging-related phenotypes. This is the first confirmation of the effectiveness of an anti-aging material using this test method (Fig. 2).
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Figure 1. Small intestinal organoids in which cellular senescence was induced
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Figure 2. HMOs inhibit the effects of aging
Research implications
These research results indicate the possibility of evaluating human “intestinal aging” in cell experiments, which has been difficult in the past, and are expected to advance the establishment of methods to inhibit intestinal aging.
About Kirin Holdings
Kirin Holdings Company, Limited is an international company that operates in the Food & Beverages domain (Food & Beverages businesses), Pharmaceuticals domain (Pharmaceuticals businesses), and Health Science domain (Health Science business), both in Japan and across the globe.
Kirin Holdings can trace its roots to Japan Brewery which was established in 1885. Japan Brewery became Kirin Brewery in 1907. Since then, the company expanded its business with fermentation and biotechnology as its core technologies, and entered the pharmaceutical business in the 1980s, all of which continue to be global growth centers. In 2007, Kirin Holdings was established as a pure holding company and is currently focusing on boosting its Health Science domain.
Under the Kirin Group Vision 2027 (KV 2027), a long-term management plan launched in 2019, the Kirin Group aims to become A global leader in CSV*, creating value across our world of Food & Beverages to Pharmaceuticals. Going forward, the Kirin Group will continue to leverage its strengths to create both social and economic value through its businesses, with the aim of achieving sustainable growth in corporate value.
* Creating Shared Value. Combined added value for consumers as well as for society at large.
Human iPS cell-derived research results on methods to inhibit aging using small intestinal organoids
What are small intestinal organoids?
Small intestinal organoids are a cell population consisting of intestinal stem cells and diverse intestinal cell types differentiated from stem cells, that have been reported to have a structure and function similar to the small intestine.4 In particular, small intestinal organoids differentiated from human iPS cells have been shown to enable evaluation of small intestinal functions that could not be evaluated with cultured cell lines, which are commonly used in intestinal research, and to be more similar to human organisms.5 Furthermore, the University of Tokyo has succeeded in significantly reducing the culture cost, making it possible to efficiently establish a new evaluation model by mass culture.6
4 Sato T et al., Nature, 2009, 14;459(7244):262-5.
5 Takahashi Y et al., iScience, 2022, 7;25(7):104542.
6 Takahashi Y et al., Scientific Reports, 2023, 3;13(1):5407.
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Small intestinal organoid
Research result (1): Cisplatin treatment can induce the cellular senescence of small intestinal organoids
We confirmed that treatment of monolayer-cultured small intestinal organoids with cisplatin for 5 days increased the number of cells stained by senescence-associated β-galactosidase (SA-β-gal) staining, a method for detecting cellular senescence (Fig. 1). We also evaluated gene expression levels and confirmed that cisplatin treatment increased the expression of genes related to cellular senescence and inflammation (Fig. 2).
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Figure 1. Increase in SA-β-gal stain-positive cells with cisplatin
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Figure 2. Cisplatin increases cellular senescence and inflammation-related gene expression
Research result (2): HMOs show efficacy in small intestinal organoids with cellular senescence
The effect of HMOs was evaluated in the cellular senescence model of small intestinal organoids established in (1) above, and it was confirmed that gene expression levels related to cellular senescence and inflammation were suppressed in the HMO-treated group compared to the group that was not treated with HMOs (Fig. 3).
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Figure 3. The anti-aging and anti-inflammatory effects of HMOs in the senescence model of small intestinal organoids
GALLERY
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Figure 1. Small intestinal organoids in which cellular senescence was induced
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Figure 2. HMOs inhibit the effects of aging
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Small intestinal organoid
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Figure 1. Increase in SA-β-gal stain-positive cells with cisplatin
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Figure 2. Cisplatin increases cellular senescence and inflammation-related gene expression
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Figure 3. The anti-aging and anti-inflammatory effects of HMOs in the senescence model of small intestinal organoids