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Regeneration of insulin producing cells from Human deciduous dental pulp cell derived iPS cells

Research Project

Project/Area Number 17H04412
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthodontics/Pediatric dentistry
Research InstitutionNiigata University

Principal Investigator

Saitoh Issei  新潟大学, 医歯学系, 准教授 (90404540)

Co-Investigator(Kenkyū-buntansha) 佐藤 正宏  鹿児島大学, 総合科学域総合研究学系, 教授 (30287099)
野口 洋文  琉球大学, 医学(系)研究科(研究院), 教授 (50378733)
稲田 絵美  鹿児島大学, 医歯学域鹿児島大学病院, 講師 (30448568)
中村 伸吾  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 防衛医学研究センター 医療工学研究部門, 講師 (00505323)
小田 真隆  京都薬科大学, 薬学部, 教授 (00412403)
松山 清  福岡工業大学, 工学部, 准教授 (40299540)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords乳歯 / iTS細胞 / iPS細胞 / ナイーブ幹細胞 / 膵β細胞 / 膵臓 / 歯髄細胞 / 幹細胞 / 膵幹細胞 / インスリン分泌細胞 / 歯髄幹細胞 / インスリン分泌β細胞への分化 / 1型糖尿病 / インスリン分泌β細胞 / 不死化 / 再生歯学 / 1型糖尿病 / 再生医学
Outline of Final Research Achievements

Human iPSCs (also known as EpiSCs) have limited capacity to differentiate and are slightly more differentiated than naive stem cells (NSCs). Although there are several in vitro protocols that allow iPSCs to differentiate into pancreatic lineage, data concerning generation of β-cells from these iPSCs are limited. Based on the pluripotentiality of NSCs, it was hypothesized that NSCs can differentiate into pancreatic β-cells when placed under an appropriate differentiation induction condition. We examined whether NSCs can be efficiently induced to form potentially pancreatic β cells after being subjected to an in vitro protocol. Several colonies with β-cell-specific marker expression were observed after the differentiation into β-cell lineage. Intrapancreatic grafting of the in vitro-formed β-cell foci into nude mice generated a cell mass containing insulin-producing cells, without noticeable tumorigenesis. These NSCs can be used as a promising resource for curing type 1 diabetes.

Academic Significance and Societal Importance of the Research Achievements

我々は世界で初めて、人工的に組織幹細胞を作成する技術を開発しました。この技術により生成された人工的組織特異的幹(iTS)細胞は、自己複製能を有し、また癌化を起こさないという優れた特性を持ちます。本研究では、抜けた乳歯から、膵iTS細胞を生成できることを示しました。これらの新たな分化誘導系は、1型糖尿病を治療するための有望な手法として使用できると考えられました。またこの手法は、別の組織特異的幹細胞の生成にも利用が可能であることが徐々に明らかになってきており、今後の発展が期待できる画期的な手法であると考えております。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (29 results)

All 2021 2020 2019 2018 Other

All Journal Article (22 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 22 results,  Open Access: 22 results) Presentation (4 results) (of which Int'l Joint Research: 2 results) Remarks (3 results)

  • [Journal Article] Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors2021

    • Author(s)
      Miyagi-Shiohira Chika、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 3 Pages: 454-454

    • DOI

      10.3390/jcm10030454

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreas Preservation in Modified Histidine-lactobionate Solution Is Superior to That in University of Wisconsin Solution for Porcine Islet Isolation2021

    • Author(s)
      Sakai-Yonaha Mayuko、Miyagi-Shiohira Chika、Kuwae Kazuho、Tamaki Yoshihito、Nishime Kai、Yonaha Tasuku、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Transplantation

      Volume: Publish Ahead of Print Issue: 9 Pages: 1770-1776

    • DOI

      10.1097/tp.0000000000003636

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA analysis based on a small number of manually isolated fixed cells (RNA-snMIFxC) to profile stem cells from human deciduous tooth-derived dental pulp cells2021

    • Author(s)
      Emi Inada、Issei Saitoh、Naoko Kubota、Yoko Iwase、Yuki Kiyokawa、Hirofumi Noguchi、Youichi Yamasaki、Masahiro Sato
    • Journal Title

      Biological Procedures Online.

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induced tissue-specific stem cells (iTSCs): their generation and possible use in regenerative medicine2021

    • Author(s)
      Issei Saitoh, Masahiro Sato, Yuki Kiyokawa, Emi Inada, Yoko Iwase, Natsumi Ibano, Hirofumi Noguchi
    • Journal Title

      Pharmaceutics

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel cell-permeable p38-MAPK inhibitor efficiently prevents porcine islet apoptosis and improves islet graft function.2020

    • Author(s)
      Noguchi H, Miyagi-Shiohira C, Nakashima Y, Saitoh I, Watanabe M.
    • Journal Title

      Am J Transplant.

      Volume: in press Issue: 5 Pages: 1296-1308

    • DOI

      10.1111/ajt.15740

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] piggyBac-Based Non-Viral In Vivo Gene Delivery Useful for Production of Genetically Modified Animals and Organs.2020

    • Author(s)
      Sato M, Inada E, Saitoh I, Watanabe S, Nakamura S.
    • Journal Title

      Pharmaceutics

      Volume: 12 Issue: 3 Pages: 277-277

    • DOI

      10.3390/pharmaceutics12030277

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutations in the C1 element of the insulin promoter lead to diabetic phenotypes in homozygous mice2020

    • Author(s)
      Noguchi H, Miyagi-Shiohira C, Nakashima Y, Kinjo T, Saitoh I, Watanabe M
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s42003-020-1040-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug-induced naive iPS cells exhibit better performance than primed iPS cells with respect to the ability to differentiate into pancreatic β-cell lineage2020

    • Author(s)
      Kiyokawa Y, Sato M, Noguchi H, Inada E, Iwase Y, Kubota N, Sawami T, Terunuma M, Maeda T, Hayasaki H, Saitoh I
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Issue: 9 Pages: 2838-2838

    • DOI

      10.3390/jcm9092838

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pancreas preservation in extracellular‐type p38 inhibitor‐containing solution improves islet yield for porcine islet isolation2020

    • Author(s)
      Yonaha Tasuku、Miyagi‐Shiohira Chika、Kuwae Kazuho、Tamaki Yoshihito、Nishime Kai、Sakai‐Yonaha Mayuko、Saitoh Issei、Watanabe Masami、Noguchi Hirofumi
    • Journal Title

      Xenotransplantation

      Volume: 28 Issue: 2

    • DOI

      10.1111/xen.12661

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a novel, pipette tip-aided cell cloning method for effective isolation of genome-edited porcine cell2020

    • Author(s)
      Sato M, Saitoh I, Akasaka E, Inada E
    • Journal Title

      OBM Genetics

      Volume: 5 Issue: 1 Pages: 16-16

    • DOI

      10.21926/obm.genet.2101126

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors2019

    • Author(s)
      Noguchi Hirofumi、Miyagi-Shiohira Chika、Nakashima Yoshiki、Kinjo Takao、Kobayashi Naoya、Saitoh Issei、Watanabe Masami、Shapiro A. M. James、Kin Tatsuya
    • Journal Title

      Molecular Therapy - Methods & Clinical Development

      Volume: 13 Pages: 243-252

    • DOI

      10.1016/j.omtm.2019.01.011

    • NAID

      120007004859

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of Primary Cultured Cells and Subcultured Cells Using Mouse Adipose-Derived Mesenchymal Stem Cells2019

    • Author(s)
      Nakashima Yoshiki、Nahar Saifun、Miyagi-Shiohira Chika、Kinjo Takao、Kobayashi Naoya、Saitoh Issei、Watanabe Masami、Fujita Jiro、Noguchi Hirofumi
    • Journal Title

      Stem Cells International

      Volume: 2019 Pages: 1-97

    • DOI

      10.1155/2019/7274057

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increased Expression of Cell Surface SSEA-1 is Closely Associated with Na?ve-Like Conversion from Human Deciduous Teeth Dental Pulp Cells-Derived iPS Cells2019

    • Author(s)
      Inada Emi、Saitoh Issei、Kubota Naoko、Iwase Yoko、Murakami Tomoya、Sawami Tadashi、Yamasaki Youichi、Sato Masahiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 7 Pages: 1651-1651

    • DOI

      10.3390/ijms20071651

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel preservation solution containing a JNK inhibitory peptide efficiently improves islet yield for porcine islet isolation.2019

    • Author(s)
      Noguchi H, Miyagi-Shiohira C, Nakashima Y, Ebi N, Hamada E, Tamaki Y, Kuwae K, Kitamura S, Kobayashi N, Saitoh I, Watanabe M
    • Journal Title

      Transplantation.

      Volume: 103 Issue: 2 Pages: 344-352

    • DOI

      10.1097/tp.0000000000002555

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Repeated human deciduous tooth-derived dental pulp cell reprogramming factor transfection yields multipotent intermediate cells with enhanced iPS cell formation capability2019

    • Author(s)
      Soda Miki、Saitoh Issei、Murakami Tomoya、Inada Emi、Iwase Yoko、Noguchi Hirofumi、Shibasaki Shinji、Kurosawa Mie、Sawami Tadashi、Terunuma Miho、Kubota Naoko、Terao Yutaka、Ohshima Hayato、Hayasaki Haruaki、Sato Masahiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1490-1490

    • DOI

      10.1038/s41598-018-37291-2

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of Proteins Differentially Expressed by Adipose-derived Mesenchymal Stem Cells Isolated from Immunodeficient Mice.2019

    • Author(s)
      Nakashima Y, Nahar S, Miyagi-Shiohira C, Kinjo T, Kobayashi N, Kitamura S, Saitoh I, Watanabe M, Fujita J, Noguchi H
    • Journal Title

      Int J Mol Sci

      Volume: 30 Issue: 11 Pages: 1-19

    • DOI

      10.3390/ijms20112672

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vivo Piggybac-Based Gene Delivery towards Murine Pancreatic Parenchyma Confers Sustained Expression of Gene of Interest.2019

    • Author(s)
      Sato M, Inada E, Saitoh I, Nakamura S, Watanabe S
    • Journal Title

      International Journal of Molecular Science

      Volume: 20 Issue: 13 Pages: 3116-3116

    • DOI

      10.3390/ijms20133116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Excellent Islet Yields after 18-h Porcine Pancreas Preservation by Ductal Injection, Pancreas Preservation with MK Solution, Bottle Purification, and Islet Purification Using Iodixanol with UW Solution and Iodixanol with MK Solution.2019

    • Author(s)
      Kuwae K, Miyagi-Shiohira C, Hamada E, Tamaki Y, Nishime K, Sakai M, Yonaha T, Makishi E, Saitoh I, Watanabe M, Noguchi H.
    • Journal Title

      J Clin Med.

      Volume: 8(10). Issue: 10 Pages: 1561-1561

    • DOI

      10.3390/jcm8101561

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] piggyBac Transposon-Based Immortalization of Human Deciduous Tooth Dental Pulp Cells with Multipotency and Non-Tumorigenic Potential.2019

    • Author(s)
      Inada E, Saitoh I, Kubota N, Iwase Y, Kiyokawa Y, Shibasaki S, Noguchi H, Yamasaki Y, Sato M
    • Journal Title

      International Journal of Molecular Science

      Volume: 20 Issue: 19 Pages: 4904-4904

    • DOI

      10.3390/ijms20194904

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential for Isolation of Immortalized Hepatocyte Cell Lines by Liver-Directed In Vivo Gene Delivery of Transposons in Mice.2019

    • Author(s)
      Sato M, Saitoh I, Inada E, Nakamura S, Watanabe S
    • Journal Title

      Stem Cells International

      Volume: 2 Pages: 5129526-5129526

    • DOI

      10.1155/2019/5129526

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intrapancreatic Parenchymal Cell Transplantation as a Possible Model for the Development of a Cell-based Therapy for Type I Diabetes Mellitus2018

    • Author(s)
      Sato M, Inada E, Nakamura S, Saitoh I
    • Journal Title

      OBM Transplantation

      Volume: 2 Issue: 3 Pages: 1-1

    • DOI

      10.21926/obm.transplant.1803016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modified cell-permeable JNK inhibitors efficiently prevents islet apoptosis and improves the outcome of islet transplantation.2018

    • Author(s)
      Noguchi H, Miyagi-Shiohira C, Nakashima Y, Ebi N, Hamada E, Tamaki Y, Kuwae K, Kobayashi N, Saitoh I, Watanabe M.
    • Journal Title

      Sci Rep.

      Volume: 8(1) Issue: 1 Pages: 11082-11082

    • DOI

      10.1038/s41598-018-29481-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト乳歯由来歯髄細胞における繰り返しの初期化因子遺伝子導入はiPS細胞形成能を増強した多能性中間細胞を生成する.2019

    • Author(s)
      齊藤一誠,稲田絵美,村上智哉,岩瀬陽子,黒澤美絵,清川裕貴,窪田直子,山﨑要一,早﨑治明
    • Organizer
      第57回日本小児歯科学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Naive-like conversion from human deciduous teeth dental pulp cells-derived iPS cells and the differentiation2019

    • Author(s)
      Issei Saitoh, Emi Inada, Masahiro Sato
    • Organizer
      International collaborative symposium on development of human resources in practical oral health and treatment.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Naïve-like conversion from human deciduous teeth dental pulp cells-derived iPS cells and the differentiation2019

    • Author(s)
      Issei Saitoh, Emi Inada, Masahiro Sato
    • Organizer
      International Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 初期胚特異的糖鎖抗原SSEA-1は乳歯歯髄細胞由来iPS細胞の高度未分化状態を特定するマーカーとして有用である2018

    • Author(s)
      8)稲田絵美, 齊藤一誠, 窪田直子, 村上智哉, 澤味規, 松枝一成, 早崎治明, 山崎要一
    • Organizer
      第56回日本小児歯科学会大会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 朝日大学小児歯科学分野ホームページ

    • URL

      http://scw.asahi-u.ac.jp/~ped/Toppage.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 新潟大学 大学院医歯学総合研究科 小児歯科学分野

    • URL

      http://www.dent.niigata-u.ac.jp/pedo/pedo.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] http://www.dent.niigata-u.ac.jp/pedo/pedo.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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