Gastroenterology, Hepatology and Nutrition
Takebe Lab

Takebe Research Lab

Modeling Complex Human Development Towards Therapy

On the basis of "reverse reduction-ism based approach," the Takebe Laboratory investigates:

  1. The deductive development of a complex human organoid model
  2. The multidisciplinary dissection of self-driven mechanisms of organogenesis
  3. The technology prototyping towards drug discovery/transplant applications

Through these efforts, with a major focus on foregut- and midgut-derived systems, our lab aims to contribute to human health by establishing new therapies especially for treating pediatric intractable disease.

Also, Dr Takebe holds a joint appointment at the Department of Regenerative Medicine, Yokohama City University in Japan, where he directs a translational program of human induced pluripotent stem cell (iPSC) based liver bud based approach for congenital liver disorders by developing a cGMP manufacturing platform.

Stem cell biology and organoid biology: Think Radically graphic.

Publications

Saiki, N; Nio, Y; Yoneyama, Y; Kawamura, S; Iwasawa, K; Kawakami, E; Araki, K; Fukumura, J; Sakairi, T; Kono, T; Thompson, WL; Cruz-Encarnacion, P; Chen, Y-W; Takebe, T. Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids. Nature Biomedical Engineering. 2025; 9(11):1869-1885.

Miao, Y; Pek, NM; Tan, C; Jiang, C; Yu, Z; Iwasawa, K; Shi, M; Kechele, DO; Sundaram, N; Pastrana-Gomez, V; Zorn, AM; Chen, Y-W; Guo, M; Gu, M. Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids. Cell. 2025; 188(16):4295-4313.e27.

Reza, HA; Santangelo, C; Iwasawa, K; Reza, AA; Sekiya, S; Glaser, K; Bondoc, A; Merola, J; Takebe, T. Multi-zonal liver organoids from human pluripotent stem cells. Nature. 2025; 641(8065):1258-1267.

Yoneyama, Y; Zhang, R-R; Maezawa, M; Masaki, H; Kimura, M; Cai, Y; Adam, M; Parameswaran, S; Mizuno, N; Bhadury, J; Nakauchi, H; Potter, SS; Weirauch, MT; Takebe, T. Intercellular mRNA transfer alters the human pluripotent stem cell state. Proceedings of the National Academy of Sciences of the United States of America. 2025; 122(4):e2413351122.

Yoneyama, Y; Wu, Y; Mori, K; Takebe, T. In toto biological framework: Modeling interconnectedness during human development. Developmental Cell. 2025; 60(1):8-20.

Osonoi, S; Takebe, T. Organoid-guided precision hepatology for metabolic liver disease. Journal of Hepatology. 2024; 80(5):805-821.

Kawakami, E; Saiki, N; Yoneyama, Y; Moriya, C; Maezawa, M; Kawamura, S; Kinebuchi, A; Kono, T; Funata, M; Sakoda, A; Itoh, Y; Takayama, K; Nio, Y; Takebe, T. Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19. Cell Stem Cell. 2023; 30(10):1315-1330.e10.

Kimura, M; Iguchi, T; Iwasawa, K; Dunn, A; Thompson, WL; Yoneyama, Y; Chaturvedi, P; Zorn, AM; Wintzinger, M; Quattrocelli, M; Myers, RP; Subramanian, GM; Hwa, V; Takebe, T. En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH. Cell. 2022; 185(22):4216-4232.e16.

Okabe, R; Chen-Yoshikawa, TF; Yoneyama, Y; Yokoyama, Y; Tanaka, S; Yoshizawa, A; Thompson, WL; Kannan, G; Kobayashi, E; Date, H; Takebe, T. Mammalian enteral ventilation ameliorates respiratory failure. Med. 2021; 2(6):773-783.e5.

Marsee, A; Roos, FJM; Verstegen, MMA; Gehart, H; De Koning, E; Lemaigre, F; Forbes, SJ; Peng, WC; Huch, M; Takebe, T; Vallier, L; Clevers, H; Van Der Laan, LJW; Spee, B. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell. 2021; 28(5):816-832.

Shinozawa, T; Kimura, M; Cai, Y; Saiki, N; Yoneyama, Y; Ouchi, R; Koike, H; Maezawa, M; Zhang, R-R; Dunn, A; Lewis, K; Thompson, WL; Asai, A; Takebe, T. High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell-Derived Organoids. Gastroenterology. 2021; 160(3):831-846.e10.

Koido, M; Kawakami, E; Fukumura, J; Noguchi, Y; Ohori, M; Nio, Y; Nicoletti, P; Aithal, GP; Daly, AK; Watkins, PB; Anayama, H; Dragan, Y; Shinozawa, T; Takebe, T. Polygenic architecture informs potential vulnerability to drug-induced liver injury. Nature Medicine. 2020; 26(10):1541-1548.

Han, L; Chaturvedi, P; Kishimoto, K; Koike, H; Nasr, T; Iwasawa, K; Giesbrecht, K; Witcher, PC; Eicher, A; Haines, L; Morimoto, M; Wells, JM; Takebe, T; Zorn, AM. Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis. Nature Communications. 2020; 11(1):4158.

Koike, H; Iwasawa, K; Ouchi, R; Maezawa, M; Giesbrecht, K; Saiki, N; Ferguson, A; Kimura, M; Thompson, WL; Wells, JM; Zorn, AM; Takebe, T. Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary. Nature. 2019; 574(7776):112-116.

Ouchi, R; Togo, S; Kimura, M; Shinozawa, T; Koido, M; Koike, H; Thompson, W; Karns, RA; Mayhew, CN; Mcgrath, PS; Akazawa, C; Yoshikawa, HY; Wells, JM; Takebe, T. Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids. Cell Metabolism. 2019; 30(2):374-384.e6.

Takebe, T; Wells, JM. Organoids by design. Science. 2019; 364(6444):956-959.

Takebe, T. Creativity for a cure. Nature Medicine. 2019; 25(6):868.

Takahashi, Y; Sekine, K; Kin, T; Takebe, T; Taniguchi, H. Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation. Cell reports. 2018; 23(6):1620-1629.

Camp, JG; Sekine, K; Gerber, T; Loeffler-Wirth, H; Binder, H; Gac, M; Kanton, S; Kageyama, J; Damm, G; Seehofer, D; Ayabe, H; Taniguchi, H; Takebe, T; Treutlein, B. Multilineage communication regulates human liver bud development from pluripotency. Nature. 2017; 546(7659):533-538.

Takebe, T; Enomura, M; Yoshizawa, E; Kimura, M; Koike, H; Ueno, Y; Matsuzaki, T; Yamazaki, T; Toyohara, T; Osafune, K; Nakauchi, H; Yoshikawa, HY; Taniguchi, H. Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation. Cell Stem Cell. 2015; 16(5):556-565.

Takebe, T; Sekine, K; Enomura, M; Koike, H; Kimura, M; Ogaeri, T; Zhang, R-R; Ueno, Y; Zheng, Y-W; Koike, N; Aoyama, S; Adachi, Y; Taniguchi, H. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013; 499(7459):481-484.

Fujii, T; Kurihara, Y; Tagawa, Y; Nagai, H; Yokota, C; Mizuo, H; Takebe, T. Safety and tolerability of intrarectal perfluorodecalin for enteral ventilation in a first-in-human trial. Med. 2025; 6(12):100887.

Kawamura, S; Yoneyama, Y; Saiki, N; Wu, Y; Moriya, C; Ohmura, R; Maezawa, M; Shimada, Y; Wang, Y; Mori, K; Sanada, Y; Hirata, Y; Sakuma, Y; Takebe, T. Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids. Cell Reports Medicine. 2025; 6(11):102433.

Saiki, N; Nio, Y; Yoneyama, Y; Kawamura, S; Iwasawa, K; Kawakami, E; Araki, K; Fukumura, J; Sakairi, T; Kono, T; Thompson, WL; Cruz-Encarnacion, P; Chen, Y-W; Takebe, T. Self-organization of sinusoidal vessels in pluripotent stem cell-derived human liver bud organoids. Nature Biomedical Engineering. 2025; 9(11):1869-1885.

Soussi, FEA; Brusilovsky, M; Buck, E; Bacon, WC; Dadgar, S; Fullerton, A; Durban, VM; Barrile, R; Helmrath, MA; Takebe, T; Roth, A; Kasendra, M. Autologous Organoid-T Cell Co-Culture Platform for Modeling of Immune-Mediated Drug-Induced Liver Injury. Advanced Science. 2025; 12(43):e08584.

Yamaguchi, H; Yoneyama, Y; Ichimura, K; Ohtsu, K; Soen, M; Moriya, C; Kumagai, M; Myers, RP; Subramanian, GM; Takebe, T. Reversal of ACLF and ALF using whole blood extracorporeal system combining HLA-depleted liver organoids with granulocyte-monocyte apheresis. Journal of Hepatology. 2025.

Miao, Y; Pek, NM; Tan, C; Jiang, C; Yu, Z; Iwasawa, K; Shi, M; Kechele, DO; Sundaram, N; Pastrana-Gomez, V; Zorn, AM; Chen, Y-W; Guo, M; Gu, M. Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids. Cell. 2025; 188(16):4295-4313.e27.

Krutko, M; Poling, HM; Sheth, M; Kongsomros, S; Bryan, AE; Sharma, M; Singh, A; Reza, HA; Wikenheiser-Brokamp, KA; Takebe, T; Helmrath, MA; Harris, GM; Esfandiari, L. Thermal Annealing Enhances Piezoelectricity and Regenerative Potential of PVDF-TrFE Nanofiber Scaffolds. Advanced Materials Technologies. 2025.

Fukunaga, I; Takebe, T. In vitro liver models for toxicological research. Drug Metabolism and Pharmacokinetics. 2025; 62:101478.

Kinoshita, Y; Kobayashi, E; Matsui, K; Inage, Y; Morimoto, K; Yamamoto, S; Iwai, S; Kitada, K; Iwasawa, K; Saito, Y; Kume, H; Takebe, T; Yokoo, T; Yamanaka, S. Life-supporting functional kidney replacement by integration of embryonic metanephros-bladder composite tissue transplants. Kidney International. 2025; 107(6):1051-1063.

Reza, HA; Santangelo, C; Iwasawa, K; Reza, AA; Sekiya, S; Glaser, K; Bondoc, A; Merola, J; Takebe, T. Multi-zonal liver organoids from human pluripotent stem cells. Nature. 2025; 641(8065):1258-1267.

Ashmore-Harris, C; Ayabe, H; Yoshizawa, E; Arisawa, T; Takada, Y; Takebe, T; Fruhwirth, GO. Gene editing enables non-invasive in vivo PET imaging of human induced pluripotent stem cell-derived liver bud organoids. Molecular Therapy: Methods & Clinical Development. 2025; 33(1):101406.

Jurickova, I; Dreskin, BW; Angerman, E; Bonkowski, E; Nguyen, J; Villarreal, R; Tominaga, K; Iwasawa, K; Braun, T; Takebe, T; Helmrath, MA; Haberman, Y; Wells, JM; Denson, LA. Eicosatetraynoic Acid Regulates Profibrotic Pathways in an Induced Pluripotent Stem Cell-Derived Macrophage-Human Intestinal Organoid Model of Crohn's Disease. Journal of Crohn's and Colitis. 2025; 19(2).

Liu, YJ; Kimura, M; Li, X; Sulc, J; Wang, Q; Rodríguez-López, S; Scantlebery, AML; Strotjohann, K; Gallart-Ayala, H; Vijayakumar, A; Houtkooper, RH; Subramanian, GM; Takebe, T; Auwerx, J. ACMSD inhibition corrects fibrosis, inflammation, and DNA damage in MASLD/MASH. Journal of Hepatology. 2025; 82(2):174-188.

Yoneyama, Y; Zhang, R-R; Maezawa, M; Masaki, H; Kimura, M; Cai, Y; Adam, M; Parameswaran, S; Mizuno, N; Bhadury, J; Nakauchi, H; Potter, SS; Weirauch, MT; Takebe, T. Intercellular mRNA transfer alters the human pluripotent stem cell state. Proceedings of the National Academy of Sciences of the United States of America. 2025; 122(4):e2413351122.

Murata, N; Nishii, S; Usuha, R; Kodaka, A; Fujimori, M; Sugawara, H; Kiriyama, T; Uchikado, H; Okumura, Y; Takebe, T. A Gamified N-back App for Identifying Mild-cognitive Impairment in Older Adults. JMA J. 2025; 8(1):174-182.

Yoneyama, Y; Wu, Y; Mori, K; Takebe, T. In toto biological framework: Modeling interconnectedness during human development. Developmental Cell. 2025; 60(1):8-20.

Tominaga, K; Kechele, DO; Sanchez, JG; Vales, S; Jurickova, I; Roman, L; Asai, A; Enriquez, JR; Mccauley, HA; Kishimoto, K; Zorn, AM; Helmrath, MA; Denson, LA; Wells, JM. Deriving Human Intestinal Organoids with Functional Tissue-Resident Macrophages All From Pluripotent Stem Cells. Cellular and Molecular Gastroenterology and Hepatology (CMGH). 2025; 19(4):101444.

Wu, Y; Menten, MJ; Kreitner, L; Kawamura, S; Oda, M; Hayashi, Y; Takebe, T; Rueckert, D; Mori, K. CLSMI2T3: 3D CLSM Vasculature Volume Reconstruction from A Single 2D Slice by Off-Focal Plane Signal Using Synthetic Data. In: Medical Optical Imaging and Virtual Microscopy Image Analysis. Springer Nature; 2025:108-118.

Wu, Y; Pan, J; Kawamura, S; Oda, M; Hayashi, Y; Takebe, T; Rueckert, D; Mori, K. A Deployable Microscopic Image Segmentation Look-Up Table Based on A Dilated CNN. In: Medical Optical Imaging and Virtual Microscopy Image Analysis. Springer Nature; 2025:3-13.

Lutolf, MP; Radisic, M; Beekman, J; Huh, DD; Huch, M; Turco, MY; Birgani, ZNT; Gao, D; Yao, R; Lin, H; Takebe, T. In vitro human cell-based models: What can they do and what are their limitations? Trends in Biotechnology. 2024; 42(12):1577-1582.

Poling, HM; Sundaram, N; Fisher, GW; Singh, A; Shiley, JR; Nattamai, K; Govindarajah, V; Cortez, AR; Krutko, MO; Ménoret, S; Mayhew, CN; Takebe, T; Mahe, MM; Helmrath, MA. Human pluripotent stem cell-derived organoids repair damaged bowel in vivo. Cell Stem Cell. 2024; 31(10):1513-1523.e7.

Sheth, M; Sharma, M; Lehn, M; Reza, H; Takebe, T; Takiar, V; Wise-Draper, T; Esfandiari, L. Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids. APL Bioengineering. 2024; 8(3):036106.

Kang, S-Y; Kimura, M; Shrestha, S; Lewis, P; Lee, S; Cai, Y; Joshi, P; Acharya, P; Liu, J; Yang, Y; Alsberg, E; Wells, JM; Takebe, T; Lee, M-Y. A Pillar and Perfusion Plate Platform for Robust Human Organoid Culture and Analysis. Advanced healthcare materials. 2024; 13(21):e2302502.

Kimura, M; Takebe, T. Cellotype-phenotype associations using 'organoid villages'. Trends in Endocrinology and Metabolism. 2024; 35(6):462-465.

Nishimura, T; Takebe, T. Synthetic human gonadal tissues for toxicology. Reproductive Toxicology. 2024; 126:108598.

Osonoi, S; Takebe, T. Organoid-guided precision hepatology for metabolic liver disease. Journal of Hepatology. 2024; 80(5):805-821.

Naraoka, Y; Mabuchi, Y; Kiuchi, M; Kumagai, K; Hisamatsu, D; Yoneyama, Y; Takebe, T; Akazawa, C. Quality Control of Stem Cell-Based Cultured Meat According to Specific Differentiation Abilities. Cells. 2024; 13(2).

Reza, HA; Farooqui, Z; Reza, AA; Conroy, C; Iwasawa, K; Ogura, Y; Okita, K; Osafune, K; Takebe, T. Synthetic augmentation of bilirubin metabolism in human pluripotent stem cell-derived liver organoids. Stem Cell Reports. 2023; 18(11):2071-2083.

Múnera, JO; Kechele, DO; Bouffi, C; Qu, N; Jing, R; Maity, P; Enriquez, JR; Han, L; Campbell, I; Mahe, MM; Hu, Y-C; Takebe, T; Helmrath, MA; Wells, JM. Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon. Cell Stem Cell. 2023; 30(11):1434-1451.e9.

Kawakami, E; Saiki, N; Yoneyama, Y; Moriya, C; Maezawa, M; Kawamura, S; Kinebuchi, A; Kono, T; Funata, M; Sakoda, A; Itoh, Y; Takayama, K; Nio, Y; Takebe, T. Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19. Cell Stem Cell. 2023; 30(10):1315-1330.e10.

Matsuzaki, T; Kawano, Y; Horikiri, M; Shimokawa, Y; Yamazaki, T; Okuma, N; Koike, H; Kimura, M; Kawamura, R; Yoneyama, Y; Nakauchi, H; Taniguchi, H; Takebe, T; Yoshikawa, HY. Preparation of mechanically patterned hydrogels for controlling the self-condensation of cells. STAR Protocols. 2023; 4(3):102471.

Tamaoki, N; Siebert, S; Maeda, T; Ha, N-H; Good, ML; Huang, Y; Vodnala, SK; Haro-Mora, JJ; Uchida, N; Tisdale, JF; Robey, PG; Kruhlak, MJ; Restifo, NP; Vizcardo, R. Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from induced pluripotent stem cells. Cell Reports: Methods. 2023; 3(4):100460.

Fujii, T; Yoneyama, Y; Kinebuchi, A; Ozeki, N; Maeda, S; Saiki, N; Chen-Yoshikawa, TF; Date, H; Nishiwaki, K; Takebe, T. Enteral liquid ventilation oxygenates a hypoxic pig model. iScience. 2023; 26(3):106142.

Kishimoto, K; Iwasawa, K; Sorel, A; Ferran-Heredia, C; Han, L; Morimoto, M; Wells, JM; Takebe, T; Zorn, AM. Directed differentiation of human pluripotent stem cells into diverse organ-specific mesenchyme of the digestive and respiratory systems. Nature Protocols. 2022; 17(11):2699-2719.

Kimura, M; Iguchi, T; Iwasawa, K; Dunn, A; Thompson, WL; Yoneyama, Y; Chaturvedi, P; Zorn, AM; Wintzinger, M; Quattrocelli, M; Myers, RP; Subramanian, GM; Hwa, V; Takebe, T. En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH. Cell. 2022; 185(22):4216-4232.e16.

Matsuzaki, T; Shimokawa, Y; Koike, H; Kimura, M; Kawano, Y; Okuma, N; Kawamura, R; Yoneyama, Y; Furuichi, Y; Hakuno, F; Nakauchi, H; Taniguchi, H; Takebe, T; Yoshikawa, HY. Mechanical guidance of self-condensation patterns of differentiating progeny. iScience. 2022; 25(10):105109.

Lee, IS; Takebe, T. Narrative engineering of the liver. Current Opinion in Genetics and Development. 2022; 75:101925.

Jurickova, I; Bonkowski, E; Angerman, E; Novak, E; Huron, A; Akers, G; Iwasawa, K; Braun, T; Hadar, R; Hooker, M; Takebe, T; Mollen, KP; Haberman, Y; Denson, LA. Eicosatetraynoic Acid and Butyrate Regulate Human Intestinal Organoid Mitochondrial and Extracellular Matrix Pathways Implicated in Crohn's Disease Strictures. Inflammatory Bowel Diseases. 2022; 28(7):988-1003.

Mizuno, M; Matsuzaki, T; Ozeki, N; Katano, H; Koga, H; Takebe, T; Yoshikawa, HY; Sekiya, I. Cell membrane fluidity and ROS resistance define DMSO tolerance of cryopreserved synovial MSCs and HUVECs. Stem Cell Research and Therapy. 2022; 13(1):177.

Lansing, F; Mukhametzyanova, L; Rojo-Romanos, T; Iwasawa, K; Kimura, M; Paszkowski-Rogacz, M; Karpinski, J; Grass, T; Sonntag, J; Schneider, PM; Rodriguez-Muela, N; Knöfler, R; Takebe, T; Buchholz, F. Correction of a Factor VIII genomic inversion with designer-recombinases. Nature Communications. 2022; 13(1):422.

JSPS PRIZE Recipient

Dr. Takanori Takebe was selected as one of six young Japanese researchers to receive the JSPS PRIZE. The Japan Society for the Promotion of Science (JSPS) offers this annual award to recognize and support young researchers with superlative research abilities in early stages of their careers. Recipients have the potential to become world leaders in their fields. Dr. Takebe will receive the award from the Imperial Prince of Japan in February 2019. Learn more about PRIZE

Contact Us

A photo of Takanori Takebe.

Takanori Takebe, MD
Assistant Professor, UC Department of Pediatrics

Mailing Address
Division of Gastroenterology, Hepatology and Nutrition &  Division of Developmental Biology
3333 Burnet Ave.
MLC 2010
Cincinnati, OH 45229-3039 

Lab: Location R, Room 3543 

Office: Location S, Suite S3.622

Phone: 513-803-7807 
Fax: 513-636-5581
Email: Takanori.Takebe@cchmc.org

Tiny cell, huge future image.
Click to enlarge.