ステムセルバイオテクノロジー研究グループ

研究課題

独自の灌流デバイスを開発し、細胞と足場材料からなる3次元組織に灌流可能な血管ネットワークを作製する技術を研究しています。酸素や栄養を供給して大きな組織を維持したり、試験の対象である薬剤や免疫細胞などを流し入れたりすることができます。これまでに皮膚、肝臓、腫瘍（がん）といった組織の構築実績があります。血管付き3次元組織を用いた所望の薬剤の評価、任意の組織・細胞と本技術の組み合わせによる再生医療用や食品成分・薬剤評価用の新たな組織の構築、灌流デバイスそのものの共同開発やライセンスなどの連携が可能です。

研究課題

自律神経は、心拍数、消化、呼吸、血圧、体温、代謝の調節およびストレス応答など、私たちの体内で幅広い機能をコントロールしています。近年、動物愛護の観点から、生体外でこれらの神経機能や自律神経を介した臓器間の相互作用を模倣する動物実験代替法の開発が求められています。私たちはこれまでに、ヒト幹細胞から自律神経系（交感神経、副交感神経）を誘導する方法を開発しました。本研究では、脳腸相関を含む生体の自律神経ネットワークを生体外で再現する動物実験代替法とその評価法の開発に取り組んでいます。この技術により、自律神経に対する創薬スクリーニングや機能評価、健康食品や機能性食品の開発に向けた食品成分の評価が可能です。また、任意の組織・細胞と自律神経の連関モデルの構築および評価、細胞の作製、治療等で使用する細胞の非侵襲評価といった分野での応用が期待されます。

研究課題

私たちは、様々な疾患や腫瘍などの病態モデルを作製し、マルチオミクス解析を行っています。また、複数臓器を共培養するための独自のデバイスを作製し、個体の複雑な臓器間ネットワークを生体外で模倣する技術の開発に取り組んでいます。例えば、腸で吸収された食品成分等が肝臓や脳など他の臓器に与える影響等を解析することが可能です。この解析には、プロテオームやトランスクリプトーム等のオミクス解析から得られる多階層の統合情報を用います。本培養モデルは、動物実験を行わずに機能性食品素材のシーズ評価や薬剤の安全性評価が可能であり、 物質探索・評価等で連携できます。

業績リスト

• Kusano, T; Sotani, Y; Takeda, R; Hatano, A; Kawata, K; Kano, R; Matsumoto, M; Kano, Y; Hoshino, D.
  Time-series transcriptomics reveals distinctive mRNA expression dynamics associated with gene ontology specificity and protein expression in skeletal muscle after electrical stimulation-induced resistance exercise.
  FASEB J. 2024 Nov 30;38(22):e70153. doi:10.1096/fj.202401420RR
• 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, Y; Loza, 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