A novel NFAT inhibitory peptide (RCAN-11R) provides immunosuppression.

• Project/Area Number: 26670590
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: University of the Ryukyus
• Principal Investigator: NOGUCHI Hirofumi 琉球大学, 医学(系)研究科(研究院), 教授 (50378733)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 免疫抑制剤 / 副作用 / 糖尿病 / 膵島移植 / 細胞毒性 / RCAN蛋白 / 蛋白導入法 / カルシニューリンインヒビター

Outline of Final Research Achievements

Calcineurin inhibitors have been used for the transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects such as diabetes. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells). This peptide (11R-VIVIT) did not affect insulin secretion. However, our recent study showed that 11R-VIVIT affected cell viability when used higher concentration because of VIVIT sequence. The aim of this study is to develop another safer NFAT inhibitor (RCAN-11R) without cell viability less toxic than calcineurin inhibitors. The peptide could interfere selectively with calcineurin-NFAT interaction without affecting calcineurin phosphatase activity similar to 11R-VIVIT. RCAN-11R did not affected cell viability when used as same concentration as toxic concentration of 11R-VIVIT. Therefore, RCAN-11R could be useful as a therapeutic agent that is less toxic than current drugs or 11R-VIVIT.

Research Products

• [Journal Article] Induction of tissue-specific stem cells by reprogramming factors, and tissue-specific selection. (2015)
  • Author(s): Noguchi H, Saitoh I, Tsugata T, Kataoka H, Watanabe M, Noguchi Y.
  • Journal Title: Cell Death Differ. Volume: 22 Issue: 1 Pages: 145-155
  • DOI: 10.1038/cdd.2014.132
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cryopreservation of Adipose-Derived Mesenchymal Stem Cells. (2015)
  • Author(s): Miyagi-Shiohira C, Kurima K, Kobayashi N, Saitoh I, Watanabe M, Noguchi Y, Matsushita M, Noguchi H.
  • Journal Title: Cell Med. Volume: 8 Issue: 1-2 Pages: 3-7
  • DOI: 10.3727/215517915x689100
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Choice of feeders is important when first establishing iPSCs derived from primarily cultured human deciduous tooth dental pulp cells. (2015)
  • Author(s): Saitoh I, Inada E, Iwase Y, Noguchi H, Murakami T, Soda M, Kubota N, Hasegawa H, Akasaka E, Matsumoto Y, Oka K, Yamasaki Y, Hayasaki H, Sato M
  • Journal Title: Cell Medicine Volume: 8 Issue: 1-2 Pages: 9-23
  • DOI: 10.3727/215517915x689038
  • Peer Reviewed / Open Access
• [Journal Article] Islet culture/preservation before islet transplantation. (2015)
  • Author(s): Noguchi H, Miyagi-Shiohira C, Kurima K, Kobayashi N, Saitoh I, Watanabe M, Noguchi Y, Matsushita M.
  • Journal Title: Cell Med. Volume: 8 Issue: 1-2 Pages: 25-29
  • DOI: 10.3727/215517915x689047
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Spheroid Formation and Evaluation of Hepatic Cells in a Three-Dimensional Culture Device (2015)
  • Author(s): Miyamoto Y, Ikeuchi M, Noguchi H, Yagi T, Hayashi S
  • Journal Title: Cell Medicine Volume: 8(1-2) Issue: 1-2 Pages: 47-56
  • DOI: 10.3727/215517915x689056
  • Peer Reviewed / Open Access
• [Journal Article] Potential factors for the differentiation of ES/iPS cells into insulin-producing cells. (2015)
  • Author(s): Tsugata T, Nikoh N, Kin T, Saitoh I, Noguchi Y, Ueki H, Watanabe M, Shapiro AMJ, Noguchi H.
  • Journal Title: Cell Med. Volume: 7 Issue: 2 Pages: 83-93
  • DOI: 10.3727/215517914x685178
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Three-Dimensional in vitro Hepatic Constructs Formed Using Combinatorial Tapered Stencil for Cluster Culture (TASCL) Device (2015)
  • Author(s): Y. Miyamoto, M. Ikeuchi, H. Noguchi, T. Yagi, S. Hayashi
  • Journal Title: Cell Medicine Volume: 7 Issue: 2 Pages: 67-74
  • DOI: 10.3727/215517914x685187
  • Peer Reviewed / Open Access
• [Journal Article] Islet Purification for Clinical Islet Transplantation. (2014)
  • Author(s): Noguchi H
  • Journal Title: Current Tissue Engineering. Volume: 3 Issue: 1 Pages: 34-38
  • DOI: 10.2174/2211542002666131230234825
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A new method for generating insulin-secreting cells from human pancreatic epithelial cells after islet isolation transformed by NeuroD1. (2014)
  • Author(s): Shimoda M, Chen S, Noguchi H, Takita M, Sugimoto K, Itoh T, Chujo D, Iwahashi S, Naziruddin B, Levy MF, Matsumoto S, Grayburn PA.
  • Journal Title: Hum Gene Ther Methods. Volume: 25 Issue: 3 Pages: 206-219
  • DOI: 10.1089/hgtb.2013.122
  • Peer Reviewed
• [Journal Article] Establishment of a pancreatic stem cell line from fibroblast-derived induced pluripotent stem cells. (2014)
  • Author(s): Kuise T, Noguchi H, Tazawa H, Kawai T, Iwamuro M, Saitoh I, Kataoka HU, Watanabe M, Noguchi Y, Fujiwara T.
  • Journal Title: Biomed Eng Online. Volume: 13 Issue: 1
  • DOI: 10.1186/1475-925x-13-64
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel positively charged nanoparticle labeling for in vivo imaging of adipose tissue-derived stem cells. (2014)
  • Author(s): Yukawa H, Nakagawa S, Yoshizumi Y, Watanabe M, Saito H, Miyamoto Y, Noguchi H, Oishi K, Ono K, Sawada M, Kato I, Onoshima D, Obayashi M, Hayashi Y, Kaji N, Ishikawa T, Hayashi S, Baba Y.
  • Journal Title: PLoS One. Volume: 9 Issue: 11 Pages: e110142-e110142
  • DOI: 10.1371/journal.pone.0110142
  • Peer Reviewed / Open Access