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Optimization of human amniotic fluid stem cell therapy for cerebral palsy

Research Project

Project/Area Number 18K15730
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKeio University

Principal Investigator

OCHIAI Daigo  慶應義塾大学, 医学部(信濃町), 講師 (80348713)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsヒト羊水幹細胞 / 間葉系幹細胞 / 脳性麻痺 / 脳室周囲白質軟化症 / 低酸素虚血性脳症 / 細胞凝集体 / 早産 / 再生医療 / 幹細胞治療 / 羊水 / 幹細胞
Outline of Final Research Achievements

Neuronal hypoxic damages induced by cerebral ischemia during delivery evoke hypoxic ischemic encephalopathy and periventricular leukomalacia(PVL), which leads to cerebral palsy characterized by irreversible neuronal damages.
In this study, we investigated the effect of intraperitoneal administration of human amniotic fluid stem cell (hAFSC) on rat model of PVL and found that hAFSC could reduce neuroinflammation and prevent the progression from PVL to cerebral palsy. We also found that hAFSCs aggregated in the peritoneal cavity and might enhance their effect.

Academic Significance and Societal Importance of the Research Achievements

脳性麻痺は現時点で有効な治療法の存在しない周産期難治性神経疾患である.ヒト羊水幹細胞は胎児から樹立可能な間葉系幹細胞の一種であり,抗炎症作用があることが知られている.我々はこれまでに,低酸素虚血性脳症モデルマウスに羊水幹細胞を経鼻投与することで一定の治療効果を見出してきた.今回,我々は類似のモデルである脳室周囲白質軟化症モデルラットに対して,ヒト羊水幹細胞を腹腔内投与することで,細胞が腹腔内で凝集体を形成し,これにより全身の炎症が抑制されて脳障害が予防される可能性を見出した.この知見は,脳性麻痺に対する革新的な治療法になる可能性があると自負しており,今後のさらなる発展が望まれる.

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (25 results)

All 2019 2018

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (16 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion2019

    • Author(s)
      Abe Yushi、Ochiai Daigo、Masuda Hirotaka、Sato Yu、Otani Toshimitsu、Fukutake Marie、Ikenoue Satoru、Miyakoshi Kei、Okano Hideyuki、Tanaka Mamoru
    • Journal Title

      STEM CELLS Translational Medicine

      Volume: 8 Issue: 11 Pages: 1170-1179

    • DOI

      10.1002/sctm.19-0002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycemic and metabolic features in gestational diabetes: singleton <i>versus</i> twin pregnancies2019

    • Author(s)
      Akiba Y, Miyakoshi K, Ikenoue S, Saisho Y, Kasuga Y, Ochiai D, Matsumoto T, Tanaka M.
    • Journal Title

      Endocrine Journal

      Volume: 66 Issue: 7 Pages: 647-651

    • DOI

      10.1507/endocrj.EJ18-0575

    • NAID

      130007684328

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human amniotic fluid stem cells have a unique potential to accelerate cutaneous wound healing with reduced fibrotic scarring like a fetus.2019

    • Author(s)
      Fukutake M, Ochiai D, Masuda H, Abe Y, Sato Y, Otani T, Sakai S, Aramaki-Hattori N, Shimoda M, Matsumoto T, Miyakoshi K, Kanai Y, Kishi K, Tanaka M.
    • Journal Title

      Hum Cell.

      Volume: 32 Issue: 1 Pages: 51-63

    • DOI

      10.1007/s13577-018-0222-1

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 分娩後に急性腎不全を発症し非典型溶血性尿毒症症候群(aHUS)と診断した1例2019

    • Author(s)
      竹田将人,池ノ上学,坂井健良,遠藤豊英,大石真希,落合大吾,宮越敬,田中守,青木大輔
    • Journal Title

      東京産科婦人科学会会誌

      Volume: 68 Pages: 339-343

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The neurorestorative effect of human amniotic fluid stem cells on the chronic phase of neonatal hypoxic-ischemic encephalopathy in mice.2019

    • Author(s)
      Otani T, Ochiai D, Masuda H, Abe Y, Fukutake M, Matsumoto T, Miyakoshi K, Tanaka M.
    • Journal Title

      Pediatr Res.

      Volume: 85 Issue: 1 Pages: 97-104

    • DOI

      10.1038/s41390-018-0131-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired fetal growth in mothers with inadequate gestational weight gain: a retrospective study in Japanese uncomplicated pregnancy.2018

    • Author(s)
      Ikenoue S, Miyakoshi K, Kasuga Y, Ochiai D, Matsumoto T, Tanaka M.
    • Journal Title

      J Matern Fetal Neonatal Med.

      Volume: 2 Issue: 13 Pages: 1-5

    • DOI

      10.1080/14767058.2018.1545835

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical and genetic characteristics of abnormal glucose tolerance in Japanese women in the first year after gestational diabetes mellitus.2018

    • Author(s)
      Kasuga Y, Miyakoshi K, Tajima A, Saisho Y, Ikenoue S, Ochiai D, Matsumoto T, Arata N, Hata K, Tanaka M.
    • Journal Title

      J Diabetes Investig.

      Volume: 印刷中 Issue: 3 Pages: 817-826

    • DOI

      10.1111/jdi.12935

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Amniotic Fluid Stem Cells: Therapeutic Potential for Perinatal Patients with Intractable Neurological Disease2018

    • Author(s)
      Ochiai D, Masuda H, Abe Y, Otani T, Fukutake M, Matsumoto T, Miyakoshi K, Tanaka M
    • Journal Title

      The Keio Journal of Medicine

      Volume: 67 Issue: 4 Pages: 57-66

    • DOI

      10.2302/kjm.2017-0019-IR

    • NAID

      130007552319

    • ISSN
      0022-9717, 1880-1293
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of Maternal Factors with Perinatal Complications in Pregnancies Complicated with Diabetes: A Single-Center Retrospective Analysis.2018

    • Author(s)
      Endo S, Saisho Y, Miyakoshi K, Ochiai D, Matsumoto T, Kawano Y, Mitsuishi M, Irie J, Tanaka M, Meguro S, Tanaka M, Itoh H.
    • Journal Title

      J Clin Med

      Volume: 7 Issue: 1 Pages: 5-5

    • DOI

      10.3390/jcm7010005

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The therapeutic potentials of human amniotic fluid stem cells on the chronic phase of neonatal hypoxic-ischemic encephalopathy2019

    • Author(s)
      Otani T,Ochiai D,Abe Y,Endo T,Oishi M,Sato Y,Fukutake M,Ikenoue S,Masuda H,Miyakoshi K,Tanaka M,Aoki D
    • Organizer
      第71回日本産科婦人科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 三次元スフェア培養はヒト羊水幹細胞の抗炎症性サイトカイン分泌と未分化マーカー発現を増強する2019

    • Author(s)
      佐藤佑,落合大吾,阿部雄志,遠藤豊英,大石真希,大谷利光,福武麻里絵,池ノ上学,升田博隆,宮越敬,田中守,青木大輔
    • Organizer
      第71回日本産科婦人科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト羊水幹細胞投与はLPS誘発性新生仔炎症モデルラットの予後を改善する2019

    • Author(s)
      佐藤佑,落合大吾,大谷利光,福武麻里絵,池ノ上学,宮越敬,田中守
    • Organizer
      第55回日本周産期・新生児医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A novel strategy to treat fetal myelomeningocele using human amniotic fluid stem cells2019

    • Author(s)
      Sato Y,Ochiai D,Abe Y,OtaniT,Fukutake M,Ikenoue S,Masuda H,Miyakoshi K,Tanaka M
    • Organizer
      RCOG World Congress 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mirror症候群に急激な血小板減少を伴った1例2019

    • Author(s)
      遠藤豊英,池ノ上学,大石真希,落合大吾,宮越敬,田中守
    • Organizer
      第55回日本周産期・新生児医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 子宮内膜異型増殖症および早期子宮体癌に対する高用量黄体ホルモン療法後妊娠の産科的予後に関する検討2019

    • Author(s)
      大石真希,宮越敬,遠藤豊英,池ノ上学,落合大吾,田中守
    • Organizer
      第55回日本周産期・新生児医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 性分化疾患を含む多発先天異常を胎内診断し周産期管理を行った1例2019

    • Author(s)
      明石一浩,池ノ上学,遠藤豊英,大石真希,落合大吾,宮越敬,田中守,長谷川奉延,飛彈麻里子,有光威志,高橋萌,若林大樹,玉岡哲,黒田達夫
    • Organizer
      第55回日本周産期・新生児医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A POTENTIAL THERAPY FOR FETAL MYELOMENINGOCELE BY HUMAN AMNIOTIC FLUID STEM CELLS.2018

    • Author(s)
      Abe Y, Ochiai D, Masuda H, Sato Y, Otani T, Fukutake M, Tanaka M
    • Organizer
      International Society for Stem Cell Research 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The therapeutic potential of human amniotic fluid stem cells on the chronic phase of neonatal hypoxic-ischemic encephalopathy in mice2018

    • Author(s)
      Otani T, Ochiai D, Masuda H, Fukutake M, Sato Y, Ikenoue S, Miyakoshi K, Tanaka M
    • Organizer
      8th Korea-Taiwan-Japan Symposium on Maternal-Fetal Medicine
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] THE THERAPEUTIC EFFECTS OF HUMAN AMNIOTIC FLUID STEM CELLS ON THE CHRONIC PHASE OF NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY2018

    • Author(s)
      Otani T, Ochiai D, Masuda H, Abe Y, Fukutake M, Sato Y, Ikenoue S, Miyakoshi K, Tanaka M
    • Organizer
      20th Congress of the Federation of Asia and Oceania Perinatal Societies (FAOPS 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A NOVEL STRATEGY TO TREAT FETAL MYELOMENINGOCELE USING HUMAN AMNIOTIC FLUID STEM CELLS2018

    • Author(s)
      Sato Y, Ochiai D, Abe Y, OtaniT, Fukutake M, Ikenoue S, Masuda H, Miyakoshi K, Tanaka M
    • Organizer
      20th Congress of the Federation of Asia and Oceania Perinatal Societies (FAOPS 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pregnancy Outcomes After Abdominal Radical Trachelectomy for Early-Stage Cervical Cancer2018

    • Author(s)
      Ochiai D, Tanaka M
    • Organizer
      2018 Kangwon-Keio International symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト羊水幹細胞を用いた脊髄髄膜瘤に対する新規胎児治療法の開発2018

    • Author(s)
      大谷利光, 落合大吾, 阿部雄志, 佐藤佑, 升田博隆, 福武麻里絵, 宮越 敬, 田中 守
    • Organizer
      第18回 日本再生医療学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ラット胎仔脊髄髄膜瘤モデルを使用したヒト羊水幹細胞の羊水腔内注入による胎児治療効果について2018

    • Author(s)
      阿部雄志, 落合大吾, 大谷利光, 福武麻里絵, 佐藤 佑, 秋葉洋平, 松本 直, 升田博隆, 宮越 敬, 田中 守, 青木大輔
    • Organizer
      第70回 日本産科婦人科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新生仔低酸素虚血性脳症モデルマウスに対するヒト羊水幹細胞鼻腔内投与の治療効果に関する検討2018

    • Author(s)
      大谷利光, 落合大吾, 阿部雄志, 福武 麻里絵, 佐藤 佑, 秋葉洋平, 松本 直, 升田博隆, 宮越 敬, 田中 守, 青木大輔
    • Organizer
      第70回 日本産科婦人科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 新生仔低酸素虚血性脳症モデルマウスに対するヒト羊水幹細胞投与の治療効果に関する検討2018

    • Author(s)
      大谷利光, 落合大吾, 佐藤 佑, 福武 麻里絵, 松本 直, 宮越 敬, 田中 守
    • Organizer
      第54回 日本周産期新生児医学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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