Stem Cell Biotechnology Research Group

Research Project

We have developed a unique perfusion device and are studying the technology to create a perfusable vascular network in 3D tissues composed of cells and scaffold materials. The device can maintain large tissues by supplying oxygen and nutrients, and can also be used to infuse drugs, immune cells, and other substances for testing purposes. So far, we have successfully constructed tissues such as skin, liver, and tumors (cancer). We can collaborate on the evaluation of desired drugs using vascularized 3D tissues, the construction of new tissues for regenerative medicine or food ingredient or drug evaluation by combining any tissue or cell with this technology, and the joint development and licensing of the perfusion device itself.

Research Project

The autonomic nervous system regulates functions like heart rate, digestion, and stress response. Recently, there's a push for animal experiment alternatives that mimic these functions and organ interactions in vitro, considering animal welfare. We've developed a method to induce the autonomic system (sympathetic and parasympathetic nerves) from human stem cells. Our study focuses on developing and evaluating in vitro methods to replicate the body's autonomic network, including brain-gut connections. This technology allows for drug screening on the autonomic nervous system and evaluating ingredients for health and functional foods. It also has potential applications in building models of tissue/cell interactions, cell production, and non-invasive cell evaluations for treatment and manufacturing.

Research Project

We are engaged in the creation of various disease and tumor models, performing multi-omics analyses. Additionally, we have developed a unique device for co-culturing multiple organs, working on technology to mimic the complex inter-organ networks of an organism ex vivo. For instance, this system can analyze how food components absorbed in the intestines affect other organs such as the liver and brain. This analysis uses integrated multi-layered information obtained from omics analyses such as proteomics and transcriptomics. Our culture model enables the evaluation of functional food ingredients and drug safety without the need for animal testing. This model is suitable for collaboration in the discovery and assessment of candidates for drugs and foods.

Results

• Kumagai, Y.
  BootCellNet, a resampling-based procedure, promotes unsupervised identification of cell populations via robust inference of gene regulatory networks.
  PLOS COMPUT BIOL. 2024 Sep 30;20(9):e1012480. doi: 10.1371/journal.pcbi.1012480
• Kano, R; Kusano, T; Takeda, R; Shirakawa, H; Poole, DC; Kano, Y; Hoshino, D.
  Eccentric contraction increases hydrogen peroxide levels and alters gene expression through Nox2 in skeletal muscle of male mice.
  J APPL PHYSIOL (1985). 2024 Jul 25. doi: 10.1152/japplphysiol.00335.2024
• Akagi, Y; Norimoto, A; Kawamura, T; Kida, YS.
  Label-Free Assessment of Neuronal Activity Using Raman Micro-Spectroscopy.
  MOLECULES. 2024 Jul 3;29(13):3174. doi: 10.3390/molecules29133174
• Song, X; Nihashi, Y; Imai, Y; Mori, N; Kagaya, N; Suenaga, H; Shin-Ya, K; Yamamoto, M; Setoyama, D; Kunisaki Y; Kida, YS .
  Collagen Lattice Model, Populated with Heterogeneous Cancer-Associated Fibroblasts, Facilitates Advanced Reconstruction of Pancreatic Cancer Microenvironment.
  INT J MOL SCI. 2024 Mar 27;25(7):3740. doi: 10.3390/ijms25073740
• Sun, L; Morikawa, K; Sogo, Y; Sugiura, Y.
  MHY1485 potentiates immunogenic cell death induction and anti-cancer immunity following irradiation.
  J RADIAT RES. 2024 Feb 8:rrad107. doi: 10.1093/jrr/rrad107
• Kishimoto, T; Nishimura, K; Morishita, K; Fukuda, A; Miyamae, Y; Kumagai, Y; Sumaru, K; Nakanishi, M; Hisatake, K; Sano, M.
  An engineered ligand-responsive Csy4 endoribonuclease controls transgene expression from Sendai virus vectors.
  J BIOL ENG. 2024 Jan 16;18(1):9. doi: 10.1186/s13036-024-00404-9
• Zhang, Y; Yang, W; Kumagai, YLoza, M; Zhang, W; Park, SJ; Nakai, K.
  Multi-omics computational analysis unveils the involvement of AP-1 and CTCF in hysteresis of chromatin states during macrophage polarization.
  FRONT IMMUNOL. 2023 Dec 20;14:1304778. doi: 10.3389/fimmu.2023.1304778
• Song, X; Nihashi, Y; amamoto, M; Setoyama, D; Kunisaki, Y; Kida, YS.
  Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model.
  BIOENGINEERING (Basel). 2023 Dec 18;10(12):1437. doi: 10.3390/bioengineering10121437
• Akagi, Y; Takayama, Y; Nihashi, Y; Yamashita, A; Yoshida, R; Miyamoto, Y; Kida, YS.
  Functional engineering of human iPSC-derived parasympathetic neurons enhances responsiveness to gastrointestinal hormones.
  FEBS OPEN BIO. 2023 Nov 27. doi: 10.1002/2211-5463.13741
• Ishioka, M; Nihashi, Y; Sunagawa, Y; Umezawa, K; Shimosato, T; Kagami, H; Morimoto, T; Takaya, T.
  Myogenetic Oligodeoxynucleotide Induces Myocardial Differentiation of Murine Pluripotent Stem Cells.
  INT J MOL SCI. 2023 Sep 21;24(18):14380. doi: 10.3390/ijms241814380
• Nihashi, Y, Song, X; Yamamoto, M; Setoyama, D; Kida, YS.
  Decoding Metabolic Symbiosis between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts Using Cultured Tumor Microenvironment.
  INT J MOL SCI. 2023 Jul 3;24(13):11015. doi: 10.3390/ijms241311015
• Takayama, Y, Akagi, Y, Kida, YS.
  Deciphering the Molecular Mechanisms of Autonomic Nervous System Neuron Induction through Integrative Bioinformatics Analysis.
  INT J MOL SCI. 2023 May 21;24(10):9053. doi: 10.3390/ijms24109053
• Kumagai, Y; Saito, Y; Kida, YS.
  A multiomics atlas of brown adipose tissue development over time.
  ENDOCRINOLOGY. 2023 Apr 21:bqad064. doi: 10.1210/endocr/bqad064
• Sogo, T; Nakao, S; Tsukamoto, T; Ueyama, T; Harada, Y; Ihara, D; Ishida, T; Nakahara, M; Hasegawa, K; Akagi, Y; Kida, YS; Nakagawa, O; Nagamune, T; Kawahara, M; Kawamura, T.
  Canonical Wnt signaling activation by chimeric antigen receptors for efficient cardiac differentiation from mouse embryonic stem cells.
  INFLAMM REGEN. 2023 Feb 10;43(1):11. doi: 10.1186/s41232-023-00258-6
• Nohira, N; Shinji, S; Nakamura, S; Nihashi, Y; Shimosato, T; Takaya, T.
  Myogenetic Oligodeoxynucleotides as Anti-Nucleolin Aptamers Inhibit the Growth of Embryonal Rhabdomyosarcoma Cells.
  BIOMEDICINES. 2022 Oct 25;10(11):2691. doi: 10.3390/biomedicines10112691
• Imai, Y;Mori, N; Nihashi, Y; Kumagai, Y; Shibuya, Y; Oshima, J; Sasaki, M; Sasaki, K; Aihara, Y; Sekido, M; Kida, YS.
  Therapeutic Potential of Adipose Stem Cell-Derived Conditioned Medium on Scar Contraction Model.
  BIOMEDICINES. 2022 Sep 24;10(10):2388. doi: 10.3390/biomedicines10102388
• Sugisawa, E; Kondo, T; Kumagai, Y; Kato, H; Takayama, Y; Isohashi, K; Shimosegawa, E; Takemura, N; Hayashi, Y; Sasaki, T; Martino, MM; Tominaga, M; Maruyama, K.
  Nociceptor-derived Reg3γ prevents endotoxic death by targeting kynurenine pathway in microglia.
  CELL REP. 2022 Mar 8;38(10):110462. doi: 10.1016/j.celrep.2022.110462
• Miyazaki, Y; Mori, N; Akagi, Y; Oda, T; Kida, YS.
  Potential Metabolite Markers for Pancreatic Cancer Identified by Metabolomic Analysis of Induced Cancer-Associated Fibroblasts.
  CANCERS. 2022 Mar 8;14(6):1375. doi: 10.3390/cancers14061375
• Akagi, Y; Mori, N; Kawamura, T; Takayama, Y; Kida, YS.
  Non-invasive cell classification using the Paint Raman Express Spectroscopy System (PRESS)
  SCI REP. 2021 Apr 23;11(1):8818. doi: 10.1038/s41598-021-88056-3
• Mori, N; Kida, YS.
  Applicability of Artificial Vascularized Liver Tissue to Proteomic Analysis.
  MICROMACHINES (Basel). 2021 Apr 11;12(4):418. doi: 10.3390/mi12040418
• Miyazaki Y, Oda T, Inagaki Y, Kushige H, Saito Y, Mori N, Takayama Y, Kumagai Y, Mitsuyama T, Kida YS
  Adipose-derived mesenchymal stem cells differentiate into heterogeneous cancer-associated fibroblasts in a stroma-rich xenograft model.
  SCI REP. 2021 Feb 25;11(1):4690. doi: 10.1038/s41598-021-84058-3
• Kumagai Y, Hirasawa T, Wachi M
  Requirement of the LtsA Protein for Formation of the Mycolic Acid-Containing Layer on the Cell Surface of Corynebacterium glutamicum.
  MICROORGANISMS. 2021 Feb 16;9(2):409. doi: 10.3390/microorganisms9020409
• Baba T, Takagi T, Sumaru K, Kanamori T, Dewa T, Nango M
  Membrane properties of ether-type phosphatidylcholine bearing partially fluorinated C(18)-monoacetylenic chains and their applicability to membrane protein reconstitution matrices
  Colloids Surf B Biointerfaces. 2020 Nov 13:111459. doi: 10.1016/j.colsurfb.2020.111459
• Takayama Y, Akagi Y, Shibuya Y, Kida YS
  Exposure to small molecule cocktails allows induction of neural crest lineage cells from human adipose-derived mesenchymal stem cells
  PLoS One. ;15(10):e0241125. (2020)doi: 10.1371/journal.pone.0241125
• Miyazaki Y, Oda T, Mori N, Kida YS
  Adipose-derived mesenchymal stem cells differentiate into pancreatic cancer-associated fibroblasts in vitro
  FEBS Open Bio. 2020 Sep 15. (2020) doi: 10.1002/2211-5463.12976
• Mori N, Kida YS
  Expression of genes involved in drug metabolism differs between perfusable 3D liver tissue and conventional 2D-cultured hepatocellular carcinoma cells
  FEBS Open Bio. 0 (2020) Aug 14. doi: 10.1002/2211-5463.12948
• Maruyama K, Kidoya H, Takemura N, Sugisawa E, Takeuchi O, Kondo T, Eid MMA, Tanaka H, Martino MM, Takakura N, Takayama Y, Akira S, Vandenbon A, Kumagai Y
  Zinc Finger Protein St18 Protects against Septic Death by Inhibiting VEGF-A from Macrophages
  Cell Rep. 32: 107906 (2020) doi:10.1016/j.celrep.2020.107906
• Sugisawa E, Takayama Y, Takemura N, Kondo T, Hatakeyama S, Kumagai Y, Sunagawa M, Tominaga M, Maruyama K
  RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis
  Cell. 8674: 30754-6 (2020) doi:10.1016/j.cell.2020.06.022
• Takayama Y, Kushige H, Akagi Y, Suzuki Y, Kumagai Y, Kida YS^*
  Selective induction of Human Autonomic neurons enables precise control of cardiomyocyte Beating
  Sci Rep.10: 9464 (2020) doi:10.1038/s41598-020-66303-3
• Mori N, Akagi Y, Imai Y, Takayama Y, Kida YS^*
  Fabrication of Perfusable Vascular Channels and Capillaries in 3D Liver-like Tissue
  Sci Rep. 10: 5646 (2020) doi: 10.1038/s41598-020-62286-3
• Baba T, Takagi T, Sumaru K, Kanamori T
  Effect of the fluorination degree of partially fluorinated octyl-phosphocholine surfactants on their interfacial properties and interactions with purple membrane as a membrane protein model
  Chemistry And Physics Lipids 227 0: 0 (2020) doi: 10.1016/j.chemphyslip.2020.104870
• Marx U, Akabane T, Andersson TB, Baker E, Beilmann M, Beken S, Brendler-Schwaab S, Cirit M, David R, Dehne EM, Durieux I, Ewart L, Fitzpatrick SC, Frey O, Fuchs F, Griffith LG, Hamilton GA, Hartung T, Hoeng J, Hogberg H, Hughes DJ, Ingber DE, Iskandar A, Kanamori T, Kojima H, Kuehnl J, Leist M, Li B, Loskill P, Mendrick DL, Neumann T, Pallocca G, Rusyn I, Smirnova L, Steger-Hartmann T, Tagle DA, Tonevitsky A, Tsyb S, Trapecar M, Van de Water B, Van den Eijnden-van Raaij J, Vulto P, Watanabe K, Wolf A, Zhou X, Roth A
  Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development
  Altex. 12: 0 (2020) doi: 10.14573/altex.2001241
• Komatsu H, Sakai K, Baba T, Takagi T, Kanamori T
  Aggregation behavior of short-chained archaeal phospholipid analogs: Contribution methyl branches to lipid hydrophobicity and membrane formability
  Colloid And Interface Science Communications 129: 3827-3832 (2019) doi: 10.1016/j.colcom.2019.100200
• Shimoaka T, Sonoyama M, Amii H, Takagi T, Kanamori T, Hasegawa T
  Raman Optical Activity on a Solid Sample: Identification of Atropisomers of Perfluoroalkyl Chains Having a Helical Conformation and No Chiral Center
  J. Physical Chemistry A 123: 3985-3991 (2019) doi: 10.1021/acs.jpca.8b11613
• Ishida S, Kanamori T
  Microphysiological system as a promising technology for drug assay
  Nihon Yakurigaku Zasshi. 154: 345-351 (2019) doi: 10.1254/fpj.154.345
• Kise R, Fukumi A, Shioya N, Shimoaka T, Sonoyama M, Amii H, , Takagi T, Kanamori T, Eda K, Hasegawa T
  Fluorous Property of a Short Perfluoroalkyl-Containing Compound Realized by Self-Assembled Monolayer Technique on a Silicon Substrate
  Bulletin The Chemical Society Japan 92: 785-789 (2019) doi: 10.1246/bcsj.20180356
• Tsukamoto T, Sogo T, Ueyama T, Nakao S, Harada Y, Ihara D, Akagi, Y, Kida YS, Hasegawa K, Nagamune T, Kawahara M*, Kawamura T*
  Chimeric G-CSF Receptor-Mediated STAT3 Activation Contributes to Efficient Induction of Cardiomyocytes from Mouse Induced Pluripotent Stem Cells
  Biotechnology J. 93: 10 (2019) doi: 10.1002/biot.201900052
• Takahashi H, Yoshino M, Morita K, Takagi T, Yokoyama Y, Kikukawa T, Amii H, Kanamori T, Sonoyama M
  Stability of the two-dimensional lattice of bacteriorhodopsin reconstituted in partially fluorinated phosphatidylcholine bilayers
  Biochim Biophys Acta Biomembr. 1861: 631-642 (2019) doi: 10.1016/j.bbamem.2018.12.015
• Hayashi Y, Matsumoto J, Kumagai S, Morishita K, Xiang L, Kobori Y, Hori S, Suzuki M, Kanamori T, Hotta K, Sumaru K
  Automated adherent cell elimination by a high-speed laser mediated by a light-responsive polymer
  Commun Biol. 1: 218 (2018) doi: 10.1038/s42003-018-0222-4
• Mori N, Morimoto Y, Takeuchi S*
  Perfusable and stretchable 3D culture system for skin-equivalent
  Biofabrication. 11: 011001 (2018) doi: 10.1088/1758-5090/aaed12
• Vandenbon A^#, Kumagai Y^#, Lin M, Suzuki Y, Nakai K^*
  Waves of chromatin modifications in mouse dendritic cells in response to LPS stimulation
  Genome Biol. 19: 138 (2018) doi: 10.1186/s13059-018-1524-z
• Maruyama K^*, Takayama Y, Sugisawa E, Yamanoi Y, Yokawa T, Kondo T, Ishibashi KI, Sahoo BR, Takemura N, Mori Y, Kanemaru H, Kumagai Y, Martino MM, Yoshioka Y, Nishijo H, Tanaka H, Sasaki A, Ohno N, Iwakura Y, Moriyama Y, Nomura M, Akira S, Tominaga M*
  The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception
  iScience. 0: 0 (2018) doi: 10.1016/j.isci.2018.08.007
• Wagatsuma A^*, Takayama Y, Hoshino T, Shiozuka M, Yamada S, Matsuda R, Mabuchi K
  Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway
  Mol Cell Biochem. 163: 170-182 (2018) doi: 10.1007/s11010-017-3250-3
• Sumaru K, Takagi T, Morishita K, Satoh T, Kanamori T
  Fabrication of pocket-like hydrogel microstructures through photolithography
  St Matter 14: 5710-5714 (2018) doi: 10.1039/c8sm00865e
• Sumaru K, Takagi T, Morishita K, Kanamori T
  Photoresponsive Aqueous Dissolution of Poly( N-Isopropylacrylamide) Functionalized with o-Nitrobenzaldehyde through Phase Transition
  Biomacromolecules. 19: 2913-2922 (2018) doi: 10.1021/acs.biomac.8b00470
• Hayashi Y, Matsumoto J, Kumagai S, Morishita K, Xiang L, Kobori Y, Hori S, Suzuki M, Kanamori T, Hotta K, Sumaru K
  Automated adherent cell elimination by a high-speed laser mediated by a light-responsive polymer
  Commun Biol. 0: 0 (2018) doi: 10.1038/s42003-018-0222-4
• Sumaru K, Takagi T, Satoh T, Kanamori T
  Photo- and Thermoresponsive Dehydration of Spiropyran-Functionalized Polymer Regulated by Molecular Recognition
  Macromol Rapid Commun. 39: 0 (2018) doi: 10.1002/marc.201700234
• Ito N, Katoh K, Kushige H, Saito Y, Umemoto T, Matsuzaki Y, Kiyonari H, Kobayashi D, Soga M, Era T, Araki N, Furuta Y, Suda T, Kida Y, Ohta K^*
  Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency
  Sci Rep. 8: 1634 (2018) doi: 10.1038/s41598-018-20057-1
• Ueyama T, Nakao S, Tsukamoto T, Ihara D, Harada Y, Akagi Y, Nakagawa S, Kida YS, Sogo T and Kawamura T^*
  PTEN/Akt Axis is Involved in Somatic Cell Reprogramming to Mouse iPS Cells
  Biomed J Sci & Tech. Res. 11: 5 (2018) DOI: 10.26717/BJSTR.2018.11.002162
• Shimoaka T, Sonoyama M, Amii H, Takagi T, Kanamori T, Hasegawa T
  Study of Perfluoroalkyl Chain-Specific Band Shift in Infrared Spectra on the Chain Length
  J. Physical Chemistry A 121: 8425-8431 (2017) doi: 10.1021/acs.jpca.7b08940
• Sumaru K, Morishita K, Takagi T, Satoh T, Kanamori T
  Sectioning of cultured cell monolayer using photo-acid-generating substrate and micro-patterned light projection
  European Polymer J. 121: 16964-16969 (2017) doi: 10.1016/j.eurpolymj.2017.02.021
• Watanabe Y, Miyasaka KY, Kubo A, Kida YS, Nakagawa O, Hirate Y, Sasaki H, Ogura T^*
  Notch and Hippo signaling converge on Strawberry Notch 1 (Sbno1) to synergistically activate Cdx2 during specification of the trophectoderm
  Sci Rep. 0: 0 (2017) doi: 10.1038/srep46135
• Kondo Y, Yada Y, Haga T, Takayama Y, Isomura T, Jimbo Y, Fukayama O, Hoshino T^*, Mabuchi K
  Temporal relation between neural activity and neurite pruning on a numerical model and a microchannel device with micro electrode array
  Biochem Biophys Res Commun. 486: 539-544 (2017) doi: 10.1016/j.bbrc.2017.03.082
• Takayama Y^#, Wakabayashi T#, Kushige H, Saito Y, Shibuya Y, Shibata S, Akamatsu W, Okano H, Kida YS^*
  Brief Exposure to Small Molecules Allows Induction of Mouse Embryonic Fibroblasts Into Neural Crest-Like Precursors
  FEBS Lett. 591: 590-602 (2017) doi: 10.1002/1873-3468.12572