• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of a Therapeutic Approach for Preterm Labor and Fetal Inflammatory Response Syndrome via Regulation of Uterine Inflammation by Human Amniotic fluid Stem Cells

Research Project

Project/Area Number 19K22602
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionKeio University

Principal Investigator

MAMORU Tanaka  慶應義塾大学, 医学部(信濃町), 教授 (20207145)

Co-Investigator(Kenkyū-buntansha) 落合 大吾  慶應義塾大学, 医学部(信濃町), 准教授 (80348713)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords羊水幹細胞 / 間葉系幹細胞 / マクロファージ / 早産 / 胎児炎症反応症候群 / ヒト羊水幹細胞 / 炎症 / 幹細胞 / 羊水
Outline of Research at the Start

世界では年1500万件の早産分娩が存在し、その主原因は子宮炎症である。子宮炎症は早産をきたすだけでなく、胎児炎症反応症候群(FIRS)も引き起こす。FIRS罹患児は胎児期に臓器障害をきたし出生後治療は困難を極める。現在、早産回避やFIRSへの治療法は無く新規治療法開発が期待されている。本研究では、早産・FIRSモデルを用い、羊水幹細胞(hAFS)が「子宮炎症の場」に遊走・生着し、抗炎症効果により早産予防やFIRS治療効果を発揮する、との仮説を検証する 。
本研究が成功すれば、患者羊水由来の幹細胞治療を用いた臨床応用が可能であり、母児にとって極めて安全な新規幹細胞治療法になると考える。

Outline of Final Research Achievements

Human amniotic fluid stem cells (hAFSCs), a type of mesenchymal stem cells (MSCs), are known to have high anti-inflammatory properties. We treated an animal model mimicking preterm birth caused by ascending infection from the cervix with hAFSCs. The therapeutic effect and some of the mechanisms were then clarified.
We also successfully obtained hAFSCs from amniotic fluid drained transvaginally from a patient with a premature rupture of the membrane.

Academic Significance and Societal Importance of the Research Achievements

これまで早産の予防法は存在しなかった。早産を引き起こす最大の原因は、膣からの上行性感染によって子宮内炎症が惹起され、増悪することである。間葉系幹細胞の一種であるヒト羊水幹細胞には、高い抗炎症作用があることが知られている。申請者らは、羊水幹細胞の持つ抗炎症作用を利用した早産予防策を検討した。
申請者らは、マウス早産モデルに羊水幹細胞を投与し、炎症反応の中心にあるマクロファージの作用を制御し、早産を予防することに成功した。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (32 results)

All 2021 2020 2019

All Journal Article (21 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 21 results,  Open Access: 13 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Clinical Results of a Massive Blood Transfusion Protocol for Postpartum Hemorrhage in a University Hospital in Japan: A Retrospective Study2021

    • Author(s)
      Ochiai Daigo、Abe Yushi、Yamazaki Rie、Uemura Tomoe、Toriumi Ayako、Matsuhashi Hiroko、Tanaka Yuya、Ikenoue Satoru、Kasuga Yoshifumi、Tanosaki Ryuji、Tanaka Mamoru
    • Journal Title

      Medicina

      Volume: 57 Issue: 9 Pages: 983-983

    • DOI

      10.3390/medicina57090983

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Efficacy of Transarterial Embolization for Postpartum Hemorrhage Complicated with Disseminated Intravascular Coagulation: A Single-Center Experience2021

    • Author(s)
      Ochiai Daigo、Nakatsuka Seishi、Abe Yushi、Ikenoue Satoru、Kasuga Yoshifumi、Inoue Masanori、Jinzaki Masahiro、Tanaka Mamoru
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10 Issue: 18 Pages: 4082-4082

    • DOI

      10.3390/jcm10184082

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deep neural network-based classification of cardiotocograms outperformed conventional algorithms2021

    • Author(s)
      Ogasawara Jun、Ikenoue Satoru、Yamamoto Hiroko、Sato Motoshige、Kasuga Yoshifumi、Mitsukura Yasue、Ikegaya Yuji、Yasui Masato、Tanaka Mamoru、Ochiai Daigo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 13367-13367

    • DOI

      10.1038/s41598-021-92805-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amniotic fluid stem cells as a novel strategy for the treatment of fetal and neonatal neurological diseases2021

    • Author(s)
      Abe Yushi、Ochiai Daigo、Sato Yu、Otani Toshimitsu、Fukutake Marie、Ikenoue Satoru、Kasuga Yoshifumi、Tanaka Mamoru
    • Journal Title

      Placenta

      Volume: 104 Pages: 247-252

    • DOI

      10.1016/j.placenta.2021.01.009

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell sheets using human amniotic fluid stem cells reduce tissue fibrosis in murine full-thickness skin wounds2021

    • Author(s)
      Ochiai Daigo、Abe Yushi、Fukutake Marie、Sato Yu、Ikenoue Satoru、Kasuga Yoshifumi、Masuda Hirotaka、Tanaka Mamoru
    • Journal Title

      Tissue and Cell

      Volume: 68 Pages: 101472-101472

    • DOI

      10.1016/j.tice.2020.101472

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prophylactic therapy with human amniotic fluid stem cells improved survival in a rat model of lipopolysaccharide-induced neonatal sepsis through immunomodulation via aggregates with peritoneal macrophages2020

    • Author(s)
      Sato Y, Ochiai D, Abe Y, Masuda H, Fukutake M, Ikenoue S, Kasuga Y, Shimoda M, Kanai Y, Tanaka M.
    • Journal Title

      Stem Cell Res Ther

      Volume: 11 Issue: 1

    • DOI

      10.1186/s13287-020-01809-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prophylactic Therapy with Human Amniotic Fluid Stem Cells Improves Long-Term Cognitive Impairment in Rat Neonatal Sepsis Survivors2020

    • Author(s)
      Abe Y, Ochiai D, Sato Y, Kanzaki S, Ikenoue S, Kasuga Y, Tanaka M.
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 24 Pages: 9590-9590

    • DOI

      10.3390/ijms21249590

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【もう胎児付属物とはいわせない!-胎盤、臍帯、羊水-】羊水幹細胞治療2020

    • Author(s)
      阿部 雄志, 落合 大吾, 田中 守
    • Journal Title

      産科と婦人科

      Volume: 87 Pages: 2073-2078

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [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 Research-status 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 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ultrasound Findings of Varices at the Site of Uterovaginal Anastomosis in a Pregnant Woman After Radical Trachelectomy2019

    • Author(s)
      Kasuga Yoshifumi、Miyakoshi Kei、Tanaka Mamoru
    • Journal Title

      Journal of Ultrasound in Medicine

      Volume: 38 Issue: 12 Pages: 3363-3364

    • DOI

      10.1002/jum.15034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transvaginal ultrasound features of the residual cervix in pregnancy after radical trachelectomy.2019

    • Author(s)
      Kasuga Yoshifumi、Miyakoshi Kei、Tanaka Mamoru
    • Journal Title

      Journal of Medical Ultrasonics

      Volume: - Issue: 2 Pages: 335-337

    • DOI

      10.1007/s10396-020-01005-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] National survey of uterine rupture in Japan: Annual report of Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2018.2019

    • Author(s)
      Makino S, Takeda S, Kondoh E, Kawai K, Takeda J, Matsubara S, Itakura A, Sago H, Tanigaki S, Tanaka M, Ikeda T, Kanayama N.
    • Journal Title

      J Obstet Gynaecol Res.

      Volume: 45 Issue: 4 Pages: 763-765

    • DOI

      10.1111/jog.13924

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The orientation of a decellularized uterine scaffold determines the tissue topology and architecture of the regenerated uterus in rats2019

    • Author(s)
      Miki Fumie、Maruyama Tetsuo、Miyazaki Kaoru、Takao Tomoka、Yoshimasa Yushi、Katakura Satomi、Hihara Hanako、Uchida Sayaka、Masuda Hirotaka、Uchida Hiroshi、Nagai Toshihiro、Shibata Shinsuke、Tanaka Mamoru
    • Journal Title

      Biology of Reproduction

      Volume: - Issue: 5 Pages: 1215-1227

    • DOI

      10.1093/biolre/ioz004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk of preterm birth after the excisional surgery for cervical lesions: a propensity-score matching study in Japan2019

    • Author(s)
      Miyakoshi Kei、Itakura Atsuo、Abe Takayuki、Kondoh Eiji、Terao Yasuhisa、Tabata Tsutomu、Hamada Hiromi、Tanaka Kyoko、Tanaka Mamoru、Kanayama Naohiro、Takeda Satoru
    • Journal Title

      The Journal of Maternal-Fetal & Neonatal Medicine

      Volume: - Issue: 6 Pages: 1-7

    • DOI

      10.1080/14767058.2019.1619687

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changes in bone metabolic profile associated with pregnancy or lactation.2019

    • Author(s)
      Miyamoto T, Miyakoshi K, Sato Y, Kasuga Y, Ikenoue S, Miyamoto K, Nishiwaki Y, Tanaka M, Nakamura M, Matsumoto M.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 6787-6787

    • DOI

      10.1038/s41598-019-43049-1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.2019

    • Author(s)
      Ogawa S, Yamada M, Nakamura A, Sugawara T, Nakamura A, Miyajima S, Harada Y, Ooka R, Okawa R, Miyauchi J, Tsumura H, Yoshimura Y, Miyado K, Akutsu H, Tanaka M, Umezawa A, Hamatani T.
    • Journal Title

      Stem Cell Reports

      Volume: 12 Issue: 6 Pages: 1366-1379

    • DOI

      10.1016/j.stemcr.2019.05.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence2019

    • Author(s)
      Sasaki Hiroyuki、Hamatani Toshio、Kamijo Shintaro、Iwai Maki、Kobanawa Masato、Ogawa Seiji、Miyado Kenji、Tanaka Mamoru
    • Journal Title

      Frontiers in Endocrinology

      Volume: 10 Pages: 811-811

    • DOI

      10.3389/fendo.2019.00811

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinctive subpopulations of the intestinal microbiota are present in women with unexplained chronic anovulation.2019

    • Author(s)
      Sasaki H, Kawamura K, Kawamura T, Odamaki T, Katsumata N, Xiao JZ, Suzuki N, Tanaka M.
    • Journal Title

      Reprod Biomed Online.

      Volume: 38 Issue: 4 Pages: 570-578

    • DOI

      10.1016/j.rbmo.2018.12.026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 生殖・周産期免疫~認識と寛容 羊水幹細胞による胎児期からの多面的な脳性麻痺の発症制御2021

    • Author(s)
      落合 大吾
    • Organizer
      第36回日本生殖免疫学会シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ヒト羊水幹細胞の腹腔内投与は腹腔内凝集体による炎症制御を介して早産を抑制する2021

    • Author(s)
      阿部 雄志, 落合 大吾, 升田 博隆, 佐藤 佑, 池ノ上 学, 春日 義史, 田中 守, 青木 大輔
    • Organizer
      第73回日本産科婦人科学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The therapeutic potentials of human amniotic fluid stem cells on neonatal sepsis model2020

    • Author(s)
      Yu Sato, Daigo Ochiai, Hirotaka Masuda, Yushi Abe, Maki Ooishi, Toshimitsu Otani, Marie Fukutake, Satoru Ikenoue, Yoshifumi Kasuga, Kei Miyakoshi, Mamoru Tanaka, Daisuke Aoki
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] 早産児敗血症モデルラットの海馬におけるアストロサイトに関する検討2020

    • Author(s)
      阿部雄志,落合大吾,升田博隆,玉川真澄,長谷川慶太,遠藤豊英,大石真希,佐藤佑,大谷利光,池ノ上学,春日義史,宮越敬,田中守,青木大輔
    • Organizer
      第72回日本産科婦人科学会学術講演会
    • Related Report
      2020 Research-status Report
  • [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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status Report

URL: 

Published: 2019-07-04   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi