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• Islet transplantation using donors after brain and cardiac death: A multicenter clinical trial in Japan

  Anazawa, T; Marubashi, S; Kodama, S; Goto, M; Eguchi, H; Maruyama, M; Shimoda, M; Noguchi, H; Yamaguchi, T; Ito, T; Kenmochi, T; Gotoh, M

  TRANSPLANTATION   107 ( 10 ) 84 - 84   2023.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Cytoprotective Effect of Pteryxin on Insulinoma MIN6 Cells Due to Antioxidant Enzymes Expression via Nrf2/ARE Activation

  Junsei Taira, Ryuji Tsuda, Chika Miyagi-Shiohira, Hirofumi Noguchi, Takayuki Ogi

  Antioxidants ( MDPI AG )  12 ( 3 ) 693 - 693   2023.03 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  The low-level antioxidant activity of pancreatic islets causes type 1 diabetes due to oxidative stress, which is also the cause of failure in the pancreatic islets' isolation and cell transplantation. In our previous study, pteryxin was found to be a natural product as a nuclear factor-erythroid-2-related factor (Nrf2) activator. This study focused on elucidation that the potentiality of pteryxin can activate the antioxidant enzymes, even under oxidative stress, by hydrogen peroxide (H2O2). Pteryxin treated with mouse insulinoma MIN6 cells was enhanced the antioxidant gene expressions in the ARE (antioxidant response element) region for HO-1 (Heme Oxygenase-1), GCLC (Glutamate-cysteine ligase catalytic subunit), SOD1 (Super Oxide dismutase1), and Trxr1 (Thioredoxin reductase1), and those enzymes were also expressed during the nuclei transference of cytoplasmic Nrf2. In fact, the cells exposed to H2O2 concentrations of a half-cell lethal in the presence of pteryxin were then induced main antioxidant enzymes, HO-1, GCLC, and Trxr1 in the ARE region. The increased glutathione (GSH) levels associated with the GCLC expression also suggested to be cytoprotective against oxidative stress by activating the redox-metabolizing enzymes involving their increased antioxidant activity in the cells. In addition, Akt is a modulator for Nrf2, which may be responsible for the Nrf2 activation. These results allowed us to consider whether pteryxin or its synthesized congeners, an Nrf2 activator, is a potential preservative agent against islet isolation during cell transplantation.

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• Protocol for the generation of human induced hepatic stem cells using Sendai virus vectors

  Noguchi, H; Nakashima, Y; Watanabe, M; Matsushita, M; Tsukahara, M; Saitoh, I; Miyagi-Shiohira, C

  STAR PROTOCOLS ( STAR Protocols )  3 ( 4 ) 101884 - 101884   2022.12 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Our recent study demonstrated the generation of induced tissue-specific stem/progenitor (iTS/iTP) cells by the transient overexpression of reprogramming factors combined with tissue-specific selection. Here, we present a protocol to reprogram human hepatocytes to generate human induced tissue-specific liver stem (iTS-L) cells. Human hepatocytes are transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and c-MYC. iTS-L cells continuously express mRNA of hepatocyte-specific markers (HNF1β and HNF4α) and do not form teratomas. For complete details on the use and execution of this protocol, please refer to Nakashima et al. (2022).1.

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• Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles

  Miyamoto, Y; Koshidaka, Y; Murase, K; Kanno, S; Noguchi, H; Miyado, K; Ikeya, T; Suzuki, S; Yagi, T; Teramoto, N; Hayashi, S

  MATERIALS ( Materials )  15 ( 21 ) 7823 - 7823   2022.11 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Establishing a rapid in vitro evaluation system for drug screening is essential for the development of new drugs. To reproduce tissues/organs with functions closer to living organisms, in vitro three-dimensional (3D) culture evaluation using microfabrication technology has been reported in recent years. Culture on patterned substrates with controlled hydrophilic and hydrophobic regions (Cell-ableTM) can create 3D liver models (miniature livers) with liver-specific Disse luminal structures and functions. MRI contrast agents are widely used as safe and minimally invasive diagnostic methods. We focused on anionic polysaccharide magnetic iron oxide nanoparticles (Resovist®) and synthesized the four types of nanoparticle derivatives with different properties. Cationic nanoparticles (TMADM) can be used to label target cells in a short time and have been successfully visualized in vivo. In this study, we examined the morphology of various nanoparticles. The morphology of various nanoparticles showed relatively smooth-edged spherical shapes. As 3D liver models, we prepared primary hepatocyte–endothelial cell heterospheroids. The toxicity, CYP3A, and albumin secretory capacity were evaluated in the heterospheroids labeled with various nanoparticles. As the culture period progressed, the heterospheroids labeled with anionic and cationic nanoparticles showed lower liver function than non-labeled heterospheroids. In the future, there is a need to improve the method of creation of artificial 3D liver or to design a low-invasive MRI contrast agent to label the artificial 3D liver.

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• Induced hepatic stem cells are suitable for human hepatocyte production

  Nakashima, Y; Miyagi-Shiohira, C; Saitoh, I; Watanabe, M; Matsushita, M; Tsukahara, M; Noguchi, H

  ISCIENCE ( iScience )  25 ( 10 ) 105052 - 105052   2022.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Human hepatocytes were transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and C-MYC to produce hepatocyte-derived induced pluripotent stem cells (iPSCs). The messenger RNA (mRNA) expression of undifferentiated markers (passage 19-21) and hepatocyte-specific markers (HSMs) (passage 0-20) in 48 established hepatocyte-derived iPSC-like colonies was examined. Among the 48 clones, 10 clones continuously expressed HSM mRNA (HNF1β and HNF4α) in passage 0-20. The colonies which expressed HSMs (iTS-L cells: induced tissue-specific stem cells from liver) showed a different tendency in microarray and methylation analyses to fibroblast-derived iPSCs (strain: 201B7). iTS-L cells were less likely to form teratomas in mice than iPSCs (He). The iTS-L cells were differentiated into hepatocyte-like cells more efficiently than iPSCs (He) or iPSCs (201B7). These data suggest that SeV expressing OCT3/4, SOX2, KLF4, and C-MYC induce the generation of iPSCs and iTS-L cells.

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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

• 組織特異的幹細胞の人工作製

  野口 洋文

  Organ Biology ( (一社)日本臓器保存生物医学会 )  25 ( 2 ) 202 - 204   2018.07  [Refereed]

   

• 【膵臓・膵島移植Up-to-Date】 膵島移植の免疫抑制法Up-to-Date

  野口 洋文, 金 達也

  胆と膵 ( 医学図書出版(株) )  38 ( 9 ) 859 - 861   2017.09  [Refereed]

   

• 心停止下膵島移植に向けた持続冷却灌流保存法による膵臓保存

  圷 尚武, 丸山 通広, 大月 和宣, 石田 健倫, 齋藤 友永, 西郷 健一, 長谷川 正行, 青山 博道, 剣持 敬, 野口 洋文

  Organ Biology ( (一社)日本臓器保存生物医学会 )  24 ( 2 ) 55 - 59   2017.07  [Refereed]

   

• 膵島移植の現況

  野口 洋文

  Organ Biology ( (一社)日本臓器保存生物医学会 )  23 ( 1 ) 29 - 32   2016.01  [Refereed]

   

  DOI

• 臨床膵島移植と細胞処理センター

  野口 洋文

  琉球医学会誌 ( 琉球医学会 )  34 ( 1-2 ) 9 - 12   2015.12  [Refereed]

   

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Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Induction of human pancreatic stem cells by novel transcription factors without Yamanaka factors

  Grant-in-Aid for Scientific Research(B)

  Project Year: 2023.04  -  2027.03 

  Direct: 14,300,000 (YEN)  Overheads: 18,590,000 (YEN)  Total: 4,290,000 (YEN)

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2023.04  -  2026.03 

  Direct: 3,700,000 (YEN)  Overheads: 4,810,000 (YEN)  Total: 1,110,000 (YEN)

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2023.04  -  2026.03 

  Direct: 3,500,000 (YEN)  Overheads: 4,550,000 (YEN)  Total: 1,050,000 (YEN)

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2022.04  -  2025.03 

  Direct: 3,200,000 (YEN)  Overheads: 4,160,000 (YEN)  Total: 960,000 (YEN)

• Induction of insulin secreting cell via human iPS cells derived from deciduous teeth using a novel organ culture method

  Grant-in-Aid for Scientific Research(B)

  Project Year: 2022.04  -  2025.03 

  Direct: 13,400,000 (YEN)  Overheads: 17,420,000 (YEN)  Total: 4,020,000 (YEN)

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