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Induction of human iTS-P and iTS-L cells using iPS cell technology

Research Project

Project/Area Number 16H05404
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionUniversity of the Ryukyus

Principal Investigator

NOGUCHI Hirofumi  琉球大学, 医学(系)研究科(研究院), 教授 (50378733)

Co-Investigator(Kenkyū-buntansha) 齊藤 一誠  新潟大学, 医歯学系, 准教授 (90404540)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords再生医療 / iTS細胞 / iPS細胞 / 体性幹細胞 / 再生医学 / iTS-P細胞 / 膵組織 / インスリン分泌細胞
Outline of Final Research Achievements

We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific stem/progenitor (iTS) cells from human pancreatic/hepatic tissue through transient expression of genes encoding the reprogramming factors OCT4, p53 shRNA, SOX2, KLF4, L-MYC, and LIN28.
Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTS cells expressing genetic markers of endoderm and tissue-specific progenitors. The iTS cells differentiated into insulin/albumin-producing cells more efficiently than human iPS cells. iTS cells subcutaneously inoculated into immunodeficient mice did not form teratomas. The generation of human iTS cells may have important implications for the clinical application of stem/progenitor cells.

Academic Significance and Societal Importance of the Research Achievements

本研究により、組織特異的幹細胞を人工的に作製することが可能であることが、ヒト細胞で証明された。この細胞の利点は1)樹立効率がiPS細胞よりも高い、2)分化誘導効率がES/iPS細胞より高い、3)奇形腫形成がなくES/iPS細胞で懸念された未分化細胞残存による腫瘍形成の心配がない、の3点である。この技術は膵・肝のみならず、さまざまな組織に関して応用可能であると考えられるため、画期的な技術であるといえる。今後、臨床応用化へ向けてiTS細胞の有効性・安全性試験を行っていきたい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (39 results)

All 2019 2018 2017 2016

All Journal Article (31 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 31 results,  Open Access: 29 results,  Acknowledgement Compliant: 5 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results)

  • [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
      2018 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
      2018 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
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adhesion characteristics of porcine pancreatic islets and exocrine tissue to coating materials2018

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

      Islets

      Volume: 10 Issue: 3 Pages: e1460294-e1460294

    • DOI

      10.1080/19382014.2018.1460294

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison Between Modified Extracellular-Type Trehalose-Containing Kyoto Solution and University of Wisconsin Solution in 18-Hour Pancreas Preservation for Islet Transplantation.2018

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

      Pancreas.

      Volume: 47(7) Issue: 7 Pages: e46-e47

    • DOI

      10.1097/mpa.0000000000001104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of Cells Cultured in DMEM 10% FBS and Chemically Defined Medium Using Human Adipose-Derived Mesenchymal Stem Cells2018

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

      International Journal of Molecular Sciences

      Volume: 19 Issue: 7 Pages: 2042-2042

    • DOI

      10.3390/ijms19072042

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
  • [Journal Article] Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA2018

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

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 12341-12341

    • DOI

      10.1038/s41598-018-30784-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Healing Effect of Human Milk Fat Globule-EGF Factor 8 Protein (MFG-E8) in A Rat Model of Parkinson’s Disease2018

    • Author(s)
      Nakashima Yoshiki、Miyagi-Shiohira Chika、Noguchi Hirofumi、Omasa Takeshi
    • Journal Title

      Brain Sciences

      Volume: 8 Issue: 9 Pages: 167-167

    • DOI

      10.3390/brainsci8090167

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Liquid Chromatography with Tandem Mass Spectrometry-Based Proteomic Analysis of the Proteins Secreted by Human Adipose-Derived Mesenchymal Stem Cells2018

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

      Cell Transplantation

      Volume: 27 Issue: 10 Pages: 1469-1494

    • DOI

      10.1177/0963689718795096

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Comparison of the Preservation of Mouse Adipose Tissue-Derived Mesenchymal Stem Cells Using the University of Wisconsin Solution and Hank’s Balanced Salt Solution2018

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

      Stem Cells International

      Volume: 2018 Pages: 1-9

    • DOI

      10.1155/2018/1625464

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Islet Purification Methods for Making a Continuous Density Gradient and Loading Tissue2018

    • Author(s)
      Ebi Nana、Miyagi-Shiohira Chika、Hamada Eri、Tamaki Yoshihito、Masamoto Mariko、Makishi Erika、Nakashima Yoshiki、Kobayashi Naoya、Saitoh Issei、Watanabe Masami、Noguchi Yasufumi、Kinjo Takao、Noguchi Hirofumi
    • Journal Title

      Cell Medicine

      Volume: 10 Pages: 215517901773309-215517901773309

    • DOI

      10.1177/2155179017733090

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Development of Cancer through the Transient Overexpression of Reprogramming Factors2018

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

      Cell Medicine

      Volume: 10 Pages: 215517901773317-215517901773317

    • DOI

      10.1177/2155179017733172

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of Egr1 on Pancreatic Endoderm Differentiation2018

    • Author(s)
      Tsugata Takako、Nikoh Naruo、Kin Tatsuya、Miyagi-Shiohira Chika、Nakashima Yoshiki、Saitoh Issei、Noguchi Yasufumi、Ueki Hideo、Watanabe Masami、Kobayashi Naoya、Shapiro Andrew M. James、Noguchi Hirofumi
    • Journal Title

      Cell Medicine

      Volume: 10 Pages: 215517901773317-215517901773317

    • DOI

      10.1177/2155179017733177

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-term Cryopreservation of Human and other Mammalian Cells at ?80 °C for 8 Years2018

    • Author(s)
      Miyamoto Yoshitaka、Ikeuchi Masashi、Noguchi Hirofumi、Hayashi Shuji
    • Journal Title

      Cell Medicine

      Volume: 10 Pages: 215517901773314-215517901773314

    • DOI

      10.1177/2155179017733148

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Comparison of Pancreatic Islet Purification using Iodixanol with University of Wisconsin Solution and with Na-Lactobionate and Histidine Solution2018

    • Author(s)
      Nakashima Yoshiki、Miyagi-Shiohira Chika、Ebi Nana、Hamada Eri、Tamaki Yoshihito、Kuwae Kazuho、Kobayashi Naoya、Saitoh Issei、Watanabe Masami、Kinjo Takao、Noguchi Hirofumi
    • Journal Title

      Cell Medicine

      Volume: 10 Pages: 215517901877507-215517901877507

    • DOI

      10.1177/2155179018775071

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Tissue Loading Before and After the Creation of a Continuous Density Gradient in Porcine Islet Purification2018

    • Author(s)
      Miyagi-Shiohira Chika、Nakashima Yoshiki、Ebi Nana、Hamada Eri、Tamaki Yoshihito、Kuwae Kazuho、Kobayashi Naoya、Saitoh Issei、Watanabe Masami、Kinjo Takao、Noguchi Hirofumi
    • Journal Title

      Cell Medicine

      Volume: 10 Pages: 215517901878134-215517901878134

    • DOI

      10.1177/2155179018781343

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of Expandable Adipose-Derived Mesenchymal Stem Cells from Aged Mesenchymal Stem Cells by a Synthetic Self-Replicating RNA.2018

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

      Int J Mol Sci.

      Volume: 6 Issue: 11 Pages: 3489-3489

    • DOI

      10.3390/ijms19113489

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Comparison of Proteins Expressed between Human and Mouse Adipose-Derived Mesenchymal Stem Cells by a Proteome Analysis through Liquid Chromatography with Tandem Mass Spectrometry2018

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

      International Journal of Molecular Sciences

      Volume: 19 Issue: 11 Pages: 3497-3497

    • DOI

      10.3390/ijms19113497

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytokines in adipose-derived mesenchymal stem cells promote the healing of liver disease2018

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

      World Journal of Stem Cells

      Volume: 10 Issue: 11 Pages: 146-159

    • DOI

      10.4252/wjsc.v10.i11.146

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induced Tissue-Specific Stem Cells and Epigenetic Memory in Induced Pluripotent Stem Cells.2018

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

      Int J Mol Sci.

      Volume: 21;19(4) Issue: 4 Pages: 930-930

    • DOI

      10.3390/ijms19040930

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation and characterization of lymphoid enhancer factor-1-positive deciduous dental pulp stem-like cells after transfection with a piggyBac vector containing LEF1 promoter-driven selection markers.2017

    • Author(s)
      Murakami T, Saitoh I, Sato M, Inada E, Soda M, Oda M, Domon H, Iwase Y, Sawami T, Matsueda K, Terao Y, Ohshima H, Noguchi H, Hayasaki H
    • Journal Title

      Archives of Oral Biology

      Volume: 81 Pages: 110-120

    • DOI

      10.1016/j.archoralbio.2017.04.033

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] RCAN-11R peptide provides immunosuppression for fully mismatched islet allografts in mice.2017

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

      Scientific Reprots.

      Volume: - Issue: 1 Pages: 3043-3043

    • DOI

      10.1038/s41598-017-02934-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK12017

    • Author(s)
      Xu Jiaqi、Sadahira Takuya、Kinoshita Rie、Li ShunAi、Huang Peng、Wada Koichiro、Araki Motoo、Ochiai Kazuhiko、Noguchi Hirofumi、Sakaguchi Masakiyo、Nasu Yasutomo、Watanabe Masami
    • Journal Title

      Oncology Letters

      Volume: 14 Pages: 5638-5642

    • DOI

      10.3892/ol.2017.6833

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A proteome analysis of pig pancreatic islets and exocrine tissue by liquid chromatography with tandem mass spectrometry.2017

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

      Islets.

      Volume: 9(6) Issue: 6 Pages: 159-176

    • DOI

      10.1080/19382014.2017.1389826

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue-Specific Stem Cells Obtained by Reprogramming of Non-Obese Diabetic (NOD) Mouse-Derived Pancreatic Cells Confer Insulin Production in Response to Glucose.2016

    • Author(s)
      Saitoh I, Sato M, Soda M, Inada E, Iwase Y, Murakami T, Ohshima H, Hayasaki H, Noguchi H.
    • Journal Title

      PLoS One.

      Volume: 11 Issue: 9 Pages: e0163580-e0163580

    • DOI

      10.1371/journal.pone.0163580

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Serum-Free, Xeno-Free Cryopreservation Solutions for Human Adipose-Derived Mesenchymal Stem Cells.2016

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

      Cell Med.

      Volume: 9 Issue: 1-2 Pages: 15-20

    • DOI

      10.3727/215517916x693122

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Evaluation of Islet Purification Methods That Use Large Bottles to Create a Continuous Density Gradient.2016

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

      Cell Med.

      Volume: 9 Issue: 1-2 Pages: 45-51

    • DOI

      10.3727/215517916x693131

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Comparison of Purification Solutions With Different Osmolality for Porcine Islet Purification.2016

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

      Cell Med.

      Volume: 9 Issue: 1-2 Pages: 53-59

    • DOI

      10.3727/215517916x693140

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enhanced Adipogenic Differentiation of Human Adipose-Derived Stem Cells in an In Vitro Microenvironment: The Preparation of Adipose-Like Microtissues Using a Three-Dimensional Culture2016

    • Author(s)
      Miyamoto Y, Ikeuchi M, Noguchi H, Yagi T, Hayashi S
    • Journal Title

      Cell Medicine

      Volume: 9(1-2) Issue: 1-2 Pages: 35-44

    • DOI

      10.3727/215517916x693096

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 糖尿病薬の可能性~膵島移植の話題も含めて~2019

    • Author(s)
      野口洋文
    • Organizer
      Diabetes Researcher’s Forum 2019
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膵島移植・再生医療の現状と展望2019

    • Author(s)
      野口洋文
    • Organizer
      '19先端医学研究交流セミナー in Okinawa
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 産業化へ向けた膵島分離技術の改変2019

    • Author(s)
      野口洋文
    • Organizer
      委託共同研究成果発表シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Modified Cell-Permeable JNK Inhibitors Effciently Prevent Islet Apoptosis2019

    • Author(s)
      Hirofumi Noguchi
    • Organizer
      The 1st Congress of Asian Pancreas and Islet Transplant Association
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 琉球大学での再生医療2019

    • Author(s)
      野口洋文
    • Organizer
      平成30年度沖縄力発見創造事業 企業誘致促進プログラム(再生医療関連)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 細胞加工施設(CPC)を利用した再生医療について2018

    • Author(s)
      野口洋文
    • Organizer
      第15回泌尿器科再建再生研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膵島移植・再生療法の現状と展望2018

    • Author(s)
      野口洋文
    • Organizer
      人工知能学会合同研究会2018
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 膵島分離におけるボトル純化法の技術改変2018

    • Author(s)
      野口洋文
    • Organizer
      第45回日本膵・膵島移植研究会
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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