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Neonatal and pediatric research on liver regenerative medicine using umbilical cord blood

Research Project

Project/Area Number 17H04229
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKyushu University

Principal Investigator

Ohga Shouichi  九州大学, 医学研究院, 教授 (60233053)

Co-Investigator(Kenkyū-buntansha) 田口 智章  九州大学, 医学研究院, 教授 (20197247)
鈴木 淳史  九州大学, 生体防御医学研究所, 教授 (30415195)
山座 孝義  九州大学, 歯学研究院, 准教授 (80304814)
長谷川 俊史  山口大学, 大学院医学系研究科, 教授 (90314806)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords間葉系細胞 / 肝様細胞 / 肝不全 / ウィルソン病 / 高チロシン血症 / 肝葉細胞 / チロシン血症 / 細胞・組織 / 移植・再生医療
Outline of Final Research Achievements

We were able to extract stem cells called "mesenchymal stem cells" that have the ability to transform into cells of various organs, such as cartilage, fat, and bone, from umbilical cord blood and naturally extracted baby teeth. We transform them into "liver-like cells" that have abilities similar to those of the liver. To develop a new treatment for congenital liver disease in children, two inherited diseases, Wilson's disease, in which copper accumulates in the liver, and hypertyrosinemia type 1, in which tyrosine, an amino acid, cannot be processed normally in the liver, were reproduced in animal models and treated with mesenchymal stem cells and liver-like cells. Liver-like and mesenchymal stem cells have been found to reduce the symptoms of these liver diseases by complementing the function of the liver and suppressing the production of hepatotoxic substances.

Academic Significance and Societal Importance of the Research Achievements

小児の先天性肝疾患には、肝移植以外に根本的な治療法がないものがいくつかある。しかし小さな体に肝移植という大きな手術は大変な負担になり、また肝臓の状態が悪いため臓器移植の負担に耐えられないことも経験する。間葉系幹細胞および間葉系幹細胞由来の肝様細胞による先天性肝疾患の治療は、肝移植に代わる新たな治療法として、あるいは根治は難しいながらも肝臓の状態を少しでも改善し、より安全に肝移植に進むための治療法として、現在の医学では治療法のない肝疾患を持ったお子さんの新たな治療の選択肢となる可能性がある。

Report

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

    (27 results)

All 2020 2019 2018 2017

All Journal Article (19 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 19 results,  Open Access: 13 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Nationwide retrospective review of hematopoietic stem cell transplantation in children with refractory Langerhans cell histiocytosis2020

    • Author(s)
      Kudo K, Maeda M, Suzuki N, Kanegane H, Ohga S, Ishii E, Shioda Y, Imamura T, Imashuku S, Tsunematsu Y, Endo M, Shimada A, Koga Y, Hashii Y, Noguchi M, Inoue M, Tabuchi K, Morimoto A
    • Journal Title

      International Journal of Hematology

      Volume: 111 Issue: 1 Pages: 137-148

    • DOI

      10.1007/s12185-019-02760-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic potential of hepatocyte-like-cells converted from stem cells from human exfoliated deciduous teeth in fulminant Wilson's disease.2019

    • Author(s)
      Junko Fujiyoshi
    • Journal Title

      Scientific Report

      Volume: 9 Issue: 1 Pages: 1535-1535

    • DOI

      10.1038/s41598-018-38275-y

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regenerative medicine using stem cells from human exfoliated deciduous teeth (SHED): a promising new treatment in pediatric surgery2019

    • Author(s)
      Taguchi T, Yanagi Y, Yoshimaru K, Zhang XY, Matsuura T, Nakayama K, Kobayashi E,Yamaza H, Nonaka K, Ohga S, Yamaza T
    • Journal Title

      Surgery Today. 2019 Apr 49(4)

      Volume: 49 Issue: 4 Pages: 316-322

    • DOI

      10.1007/s00595-019-01783-z

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elevated non-invasive liver fibrosis markers and risk of liver carcinoma in adult patients after repair of tetralogy of Fallot2019

    • Author(s)
      Yamamura K, Sakamoto I, Morihana E, Hirata Y, Nagata H, Yamasaki Y, Okumura Y, Kohashi K, Koto K, Tsutsui H, Ohga S
    • Journal Title

      International Journal of Cardiology

      Volume: 287 Pages: 121-126

    • DOI

      10.1016/j.ijcard.2019.04.032

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis2019

    • Author(s)
      Sonoda M, Ishimura M, Eguchi K, Shiraishi A, Kanno S, Kaku N, Inoue H, Motomura Y, Ochiai M, Sakai Y, Nakayama M, Ohara O, Ohga S
    • Journal Title

      Int J Hematol

      Volume: NA Issue: 1 Pages: 131-136

    • DOI

      10.1007/s12185-019-02738-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Systemic Epstein-Barr Virus-Positive T/NK Lymphoproliferative Diseases With SH2D1A/XIAP Hypomorphic Gene Variants2019

    • Author(s)
      Ishimura M, Eguchi K, Shiraishi A, Sonoda M, Azuma Y, Yamamoto H, Imadome K, Ohga S
    • Journal Title

      Frontiers in Pediatrics

      Volume: 7 Pages: 183-183

    • DOI

      10.3389/fped.2019.00183

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hemorrhagic Pneumonia as the First Manifestation of Anhidrotic Ectodermal Dysplasia with Immunodeficiency2019

    • Author(s)
      Ichimiya Y, Sonoda M, Ishimura M, Kanno S, Ohga S
    • Journal Title

      Journal of Clinical Immunology

      Volume: 39 Issue: 3 Pages: 264-266

    • DOI

      10.1007/s10875-019-00626-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Outcomes of children with hemophagocytic lymphohistiocytosis treated using HLH-2004 protocol in Japan2019

    • Author(s)
      Yanagaisawa R, Matsuda K, Ohga S, Kanegane H, Morimoto A, Saito AM, Horibe K, Ishii E, Nakazawa Y
    • Journal Title

      International Journal of Hematology

      Volume: 109 Issue: 5 Pages: 612-617

    • DOI

      10.1007/s12185-019-02612-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis.2018

    • Author(s)
      Kinjo T, Inoue H, Kusuda T, Fujiyoshi J, Ochiai M, Takahata Y, Honjo S, Koga Y, Hara T, Ohga S
    • Journal Title

      Pediatr Neonatol.

      Volume: 54 Issue: 4 Pages: 53-60

    • DOI

      10.1016/j.pedneo.2018.09.005

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The efficacy of serum brain natriuretic peptide for the early detection of portopulmonary hypertension in biliary atresia patients before liver transplantation.2018

    • Author(s)
      Yoshimaru K, Matsuura T, Takahashi Y, Yanagi Y, Nagata H, Ohga S, Taguchi T
    • Journal Title

      Pediatr Transplant. 2018 Aug;22(5):e13203.

      Volume: 22 Issue: 5 Pages: 1-9

    • DOI

      10.1111/petr.13203

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Survey of Anticancer Drug Exposure to Attendant Families in Pediatric Medical Centers.2018

    • Author(s)
      Noda Y, Koga Y, Ohta M, Miyazono M, Wakasugi Y, Funakoshi Y, Urabe Y, Kifune M, Ueda T, Oba U, Nakashima K, Souzaki R, Kinoshita Y, Taguchi T, Ohga S
    • Journal Title

      Japanese Journal of Cancer and Chemotherapy.2018 Jun;45(6):945-948

      Volume: 45 Pages: 945-948

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired neurite development associated with mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of children with autism spectrum disorder.2018

    • Author(s)
      Nguyen HTN, Kato H, Masuda K, Yamaza H, Hirofuji Y, Sato H, Phama T, Takayama F, Sakai Y,Ohga S, Taguchi T, Nonaka K
    • Journal Title

      Biochem Biophys Rep

      Volume: 16 Pages: 24-31

    • DOI

      10.1016/j.bbrep.2018.09.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fever and Skin Involvement at Diagnosis Predicting the Intractable Langerhans Cell Histiocytosis: 40 Case-Series in a Single Center.2018

    • Author(s)
      Kobayashi T, Koga Y, Ishimura M, Nakashima K, Kato W, Ono H, Sonoda M, Eguchi K, Fukano R, Honjo S, Oda Y, Ohga S
    • Journal Title

      J Pediatr Hematol Oncol. 2018 Apr;40(3):e148-e153.

      Volume: 40 Issue: 3 Pages: 148-153

    • DOI

      10.1097/mph.0000000000001080

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Posttransplant recipient-derived CD4+ T-cell lymphoproliferative disease in X-linked hyper-IgM syndrome.2018

    • Author(s)
      Hagio Y, Shiraishi A, Ishimura M, Sonoda M, Eguchi K, Yamamoto H, Oda Y, Ohga S
    • Journal Title

      Pediatr Blood Cancer. 2018 Oct 30:e27529.

      Volume: 66 Issue: 3 Pages: 1-2

    • DOI

      10.1002/pbc.27529

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nontuberculous mycobacteria-associated hemophagocytic lymphohistiocytosis in MonoMAC syndrome.2018

    • Author(s)
      Eguchi K, Ishimura M, Sonoda M, Ono H, Shiraishi A, Kanno S, Koga Y, Takada H, Ohga S.
    • Journal Title

      Pediatr Blood Cancer

      Volume: Mar 1 Issue: 7 Pages: 1-3

    • DOI

      10.1002/pbc.27017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of a child with Rett syndrome2018

    • Author(s)
      Hirofuji Saki、Hirofuji Yuta、Kato Hiroki、Masuda Keiji、Yamaza Haruyoshi、Sato Hiroshi、Takayama Fumiko、Torio Michiko、Sakai Yasunari、Ohga Shouichi、Taguchi Tomoaki、Nonaka Kazuaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 498 Issue: 4 Pages: 898-904

    • DOI

      10.1016/j.bbrc.2018.03.077

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 infection2017

    • Author(s)
      Fujimoto Y, Hasegawa S, Matsushigea T, Wakiguchi H, Nakamura T, Hasegawa H, Nakajima N, Ainai A, Oga A, Itoh H, Shirabe K, Toda S, Atsutae R, Morishima T, Ohga S
    • Journal Title

      Sci Rep 2017 Aug 22;7(1):9128.

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-017-08030-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant2017

    • Author(s)
      Yamada Yuichi、Kinoshita Izumi、Kenichi Kohashi、et al
    • Journal Title

      Histopathology

      Volume: 72 Issue: 3 Pages: 460-471

    • DOI

      10.1111/his.13377

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Successful Liver Transplantation for Transient Abnormal Myelopoiesis-Associated Liver Failure2017

    • Author(s)
      Yasuoka Kazuaki、Inoue Hirosuke、Tanaka Koichi、Fujiyoshi Junko、Matsushita Yuki、Ochiai Masayuki、Koga Yuhki、Matsuura Toshiharu、Taguchi Tomoaki、Ohga Shouichi
    • Journal Title

      Neonatology

      Volume: 112 Issue: 2 Pages: 159-162

    • DOI

      10.1159/000474930

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] HEPATOCYTE-LIKE-CELLS CONVERTED FROM STEM CELLS FROM HUMAN EXFOLIATED DECIDUOUS TEETH FOR A NOVEL CELL THERAPY FOR FULMINANT WILSON’S DISEASE2019

    • Author(s)
      Fujiyoshi J, Yamaza H, Sonoda S, Yuniartha R, Ihara K, Nonaka K, Taguchi T, Ohga S, Yamaza T
    • Organizer
      The 15th Congress of Asian Society for Pediatric Research(国際学会)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 造血・免疫不全症に対する細胞療法2019

    • Author(s)
      大賀正一
    • Organizer
      第47回千葉基礎臨床免疫セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 造血・免疫不全症に対する細胞療法~間葉系細胞療法~2019

    • Author(s)
      大賀正一
    • Organizer
      小児血液・がんセミナーin 中四国
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 小児科外来で疑う免疫不全症2019

    • Author(s)
      大賀正一
    • Organizer
      第29回日本外来小児科学会年次集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ~ 小児から成人へ ~ IBD患者の移行期ケアを考える2019

    • Author(s)
      大賀正一
    • Organizer
      IBDトランジッショナルケア連携セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Systemic EBV-positive T/NK lymphoproliferative diseases with SH2D1A/XIAP hypomorphic gene variants.2019

    • Author(s)
      Eguchi K
    • Organizer
      The 81st Annual Meeting of the Japanese Society of Hematology
    • Related Report
      2019 Annual Research Report
  • [Presentation] AYA世代発症の家族性血球貪食症候群3型2019

    • Author(s)
      矢田裕太郎,石村匡崇,沼田晃彦,江口克秀, 園田素史,白石暁,古賀友紀,大賀正一
    • Organizer
      第181回 福岡血液懇話会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 非腫瘍性疾患に対する造血細胞移植~九州大学小児科での10年間の検討~2019

    • Author(s)
      江口克秀,石村匡崇, 白石暁,幸伏寛和,長谷川一太,矢田裕太郎,園田素史,古賀友紀,大賀正一
    • Organizer
      第61回日本小児血液・がん学会
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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