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Development of umbilical cord-derived mesenchymal stem cell therapy for neonatal sepsis using a preterm mouse model

Research Project

Project/Area Number 19K17296
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Nishida Kosuke  神戸大学, 医学部附属病院, 助教 (40837697)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords新生児敗血症 / 間葉系幹細胞 / 早産児マウス敗血症モデル / 酸化ストレス / MSCs / sepsis / Neonate / マウスモデル / 炎症 / 胎児付属物 / ヒトリコンビナントトロンボモジュリン / 感染侵襲 / 早産児
Outline of Research at the Start

早産児敗血症は、全身性炎症反応に加え、複数の侵襲因子が関与する多因子疾患と考えられるが、有効な治療法はない。
間葉系幹細胞(Mesenchymal Stem Cells、以下MSCs)は傷害組織に集積し、種々の因子を放出して治療効果を発揮する点において、早産児敗血症の新規治療法として期待できる。周産期においては、胎児付属物からMSCsが分離可能であり、患児自身のMSCsを用いた早産児敗血症の治療が想定できる。
本研究では、ヒトの胎児付属物から分離・培養したMSCsを、我々が独自に確立した早産児マウス敗血症モデルに投与し、治療効果を検討することで、早産児敗血症に対する新規治療法の開発を目指す。

Outline of Final Research Achievements

The ultimate goal of this study is to examine the protective effect of umbilical cord-derived MSCs for neonatal sepsis using preterm sepsis mouse model.

The research results to date have not proved the sepsis-protective effect of MSCs administration in the adult sepsis mouse model. Whereas, we have succeeded in establishing an experimental system of oxidative stress dynamics using urine samples of sepsis model mice, and a drug treatment experimental system for preterm sepsis mouse model. Thus, we will verify the protective effect of MSCs by using these protocols in future research.

Academic Significance and Societal Importance of the Research Achievements

新生児敗血症、全身性炎症反応に加えて、酸化ストレスなどの複数の侵襲因子が関与し、従来の抗菌薬治療単独では十分な治療効果が得られていない。
一方、間葉系幹細胞(Mesenchymal Stem Cells、以下MSCs)は傷害組織に集積し、種々の因子を放出して治療効果を発揮する点において、多臓器不全を本態とする早産児敗血症の理想的な治療法といえる。本研究では、ヒト臍帯から分離・培養したMSCsを、我々が独自に確立した早産児マウス敗血症モデルに投与し治療効果を検討した。

Report

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

    (20 results)

All 2021 2020 2019

All Journal Article (18 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 17 results,  Open Access: 10 results) Presentation (2 results)

  • [Journal Article] Three cases of pseudohypoaldosteronism following ileostomy in preterm infants2021

    • Author(s)
      Nakasone Ruka、Fujioka Kazumichi、Nishida Kosuke、Nozu Kandai、Iijima Kazumoto
    • Journal Title

      Pediatrics & Neonatology

      Volume: 62 Issue: 1 Pages: 119-121

    • DOI

      10.1016/j.pedneo.2020.09.006

    • NAID

      120007006686

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bilirubin/albumin (B/A) ratios correlate with unbound bilirubin levels in preterm infants2021

    • Author(s)
      Abe Shinya、Fujioka Kazumichi、Nakasone Ruka、Suga Shutaro、Ashina Mariko、Nishida Kosuke、Wong Ronald J.、Iijima Kazumoto
    • Journal Title

      Pediatric Research

      Volume: 1 Issue: 6 Pages: 1-1

    • DOI

      10.1038/s41390-020-01351-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Changes in awareness and knowledge concerning mother-to-child infections among Japanese pregnant women between 2012 and 20182021

    • Author(s)
      Suga Shutaro、Fujioka Kazumichi、Nakasone Ruka、Abe Shinya、Fukushima Sachiyo、Ashina Mariko、Nishida Kosuke、Nozu Kandai、Iijima Kazumoto、Tanimura Kenji、Yamada Hideto
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 1 Pages: 0244945-0244945

    • DOI

      10.1371/journal.pone.0244945

    • NAID

      120006954845

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neurodevelopmental Outcomes at 18 Months of Corrected Age for Late Preterm Infants Born at 34 and 35 Gestational Weeks2021

    • Author(s)
      Nakasone Ruka、Fujioka Kazumichi、Kyono Yuki、Yoshida Asumi、Kido Takumi、Suga Shutaro、Abe Shinya、Ashina Mariko、Nishida Kosuke、Tanimura Kenji、Yamada Hideto、Nozu Kandai、Iijima Kazumoto
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 2 Pages: 640-640

    • DOI

      10.3390/ijerph18020640

    • NAID

      120006958056

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Preterm Case of Cow’s Milk Allergy Presenting with Recurrent Ascites Treated with Donor Breast Milk2021

    • Author(s)
      Nakasone Ruka、Fujioka Kazumichi、Suga Shutaro、Abe Shinya、Ashina Mariko、Nishida Kosuke、Sakurai Motoichiro、Mizuno Katsumi、Nozu Kandai、Iijima Kazumoto
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 3 Pages: 1187-1187

    • DOI

      10.3390/ijerph18031187

    • NAID

      120006975823

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recombinant human thrombomodulin attenuated sepsis severity in a non-surgical preterm mouse model2020

    • Author(s)
      Ashina Mariko、Fujioka Kazumichi、Nishida Kosuke、Okubo Saki、Ikuta Toshihiko、Shinohara Masakazu、Iijima Kazumoto
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 333-333

    • DOI

      10.1038/s41598-019-57265-2

    • NAID

      120006877475

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of Neurodevelopmental Impairment in Congenital Cytomegalovirus Infection by Early Postnatal Magnetic Resonance Imaging2020

    • Author(s)
      Nishida Kosuke?、Fujioka Kazumichi、Sugioka Yusuke、Abe Shinya、Ashina Mariko、Fukushima Sachiyo、Ohyama Shohei、Ikuta Toshihiko、Tanimura Kenji、Yamada? Hideto、Iijima Kazumoto、Morioka Ichiro
    • Journal Title

      Neonatology

      Volume: 117 Issue: 4 Pages: 460-466

    • DOI

      10.1159/000508218

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] False positive cases of elevated tetradecenoyl carnitine in newborn mass screening showed significant loss of body weight2020

    • Author(s)
      Bo Ryosuke、Awano Hiroyuki、Nishida Kosuke、Fujioka Kazumichi、Nishiyama Atsushi、Miyake Osamu、Iijima Kazumoto
    • Journal Title

      Molecular Genetics and Metabolism Reports

      Volume: 24 Pages: 100634-100634

    • DOI

      10.1016/j.ymgmr.2020.100634

    • NAID

      120006882475

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Method for Measuring Serum Unbound Bilirubin Levels Using Glucose Oxidase?Peroxidase and Bilirubin-Inducible Fluorescent Protein (UnaG): No Influence of Direct Bilirubin2020

    • Author(s)
      Iwatani Sota、Yamana Keiji、Nakamura Hajime、Nishida Kosuke、Morisawa Takeshi、Mizobuchi Masami、Osawa Kayo、Iijima Kazumoto、Morioka Ichiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 18 Pages: 6778-6778

    • DOI

      10.3390/ijms21186778

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin Therapy for Hyperglycemia in Neonatal Sepsis Using a Preterm Mouse Model2019

    • Author(s)
      Miyauchi Harunori、Fujioka Kazumichi、Okubo Saki、Nishida Kosuke、Ashina Mariko、Ikuta Toshihiko、Okata Yuichi、Maeda Kosaku、Iijima Kazumoto、Bitoh Yuko
    • Journal Title

      Pediatrics International

      Volume: - Issue: 5 Pages: 581-586

    • DOI

      10.1111/ped.14126

    • NAID

      120006864552

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diagnostic Value of Cytomegalovirus IgM Antibodies at Birth in PCR-Confirmed Congenital Cytomegalovirus Infection2019

    • Author(s)
      Ohyama Shohei、Fujioka Kazumichi、Fukushima Sachiyo、Abe Shinya、Ashina Mariko、Ikuta Toshihiko、Nishida Kosuke、Matsumoto Hisayuki、Nakamachi Yuji、Tanimura Kenji、Yamada Hideto、Iijima Kazumoto
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 13 Pages: 3239-3239

    • DOI

      10.3390/ijms20133239

    • NAID

      120006712319

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of poor neurological development in patients with symptomatic congenital cytomegalovirus diseases after oral valganciclovir treatment2019

    • Author(s)
      Fukushima Sachiyo、Morioka Ichiro、Ohyama Shohei、Nishida Kosuke、Iwatani Sota、Fujioka Kazumichi、Mandai Tsurue、Matsumoto Hisayuki、Nakamachi Yuji、Deguchi Masashi、Tanimura Kenji、Iijima Kazumoto、Yamada Hideto
    • Journal Title

      Brain and Development

      Volume: 41 Issue: 9 Pages: 743-750

    • DOI

      10.1016/j.braindev.2019.04.016

    • NAID

      120006782284

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of Valganciclovir Treatment Depends on the Severity of Hearing Dysfunction in Symptomatic Infants with Congenital Cytomegalovirus Infection2019

    • Author(s)
      Ohyama Shohei、Morioka Ichiro、Fukushima Sachiyo、Yamana Keiji、Nishida Kosuke、Iwatani Sota、Fujioka Kazumichi、Matsumoto Hisayuki、Imanishi Takamitsu、Nakamachi Yuji、Deguchi Masashi、Tanimura Kenji、Iijima Kazumoto、Yamada Hideto
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 6 Pages: 1388-1388

    • DOI

      10.3390/ijms20061388

    • NAID

      120006624227

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 第2子に偽性低アルドステロン症を認め、第1子にも高レニン・高アルドステロン血症を認めた二絨毛膜二羊膜双胎例2019

    • Author(s)
      市川 裕太, 藤岡 一路, 阿部 真也, 芦名 満理子, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠
    • Journal Title

      周産期医学

      Volume: 49 Pages: 1675-1678

    • NAID

      40022104366

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 母体の尾骨突出を認めた新生児頭蓋骨陥没骨折の2例2019

    • Author(s)
      西田 浩輔, 藤岡 一路, 森沢 猛, 米谷 昌彦, 飯島 一誠
    • Journal Title

      日本周産期・新生児医学会雑誌

      Volume: 55 Pages: 848-851

    • NAID

      120006960258

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【新生児医療67の臨床手技とケア タイミング、流れ&コツ、評価まで見える】(第2章)治療・検査の手技 (5節)検査【エコー、生理機能検査】聴性脳幹反応 ABRとaABR2019

    • Author(s)
      西田 浩輔, 森本 紗代, 藤岡 一路
    • Journal Title

      with NEO

      Volume: - Pages: 111-115

    • Related Report
      2019 Research-status Report
  • [Journal Article] 出生後初回の採血で著明な高K血症を呈した尿路奇形を伴わない続発性偽性低アルドステロン症の1新生児例2019

    • Author(s)
      市川 裕太, 藤岡 一路, 芦名 満理子, 阿部 真也, 福嶋 祥代, 生田 寿彦, 大山 正平, 西田 浩輔, 野津 寛大, 飯島 一誠
    • Journal Title

      小児科臨床

      Volume: 72 Pages: 1030-1034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 西田 浩輔, 藤岡 一路, 芦名 満理子, 阿部 真也, 福嶋 祥代, 生田 寿彦, 大山 正平, 飯島 一誠2019

    • Author(s)
      軽度の片側性水腎症に合併した続発性偽性低アルドステロン症の1新生児例
    • Journal Title

      小児科臨床

      Volume: 72 Pages: 337-341

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 当院で経験した新生児偽性低アルドステロン症(Peudohypoaldosteronism: PHA)13例の検討2019

    • Author(s)
      西田浩輔、藤岡一路、芦名満理子、阿部真也、福嶋祥代、大山正平、生田寿彦、飯島一誠
    • Organizer
      日本周産期・新生児医学会第55回学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 先天性サイトメガロウイルス感染症児における生後早期の頭部MRI所見2019

    • Author(s)
      西田浩輔、杉岡勇典、仲宗根瑠花、永井貞之、菅秀太郎、阿部真也、芦名満理子、福嶋祥代、大山正平、生田寿彦、藤岡一路、飯島一誠
    • Organizer
      第93回日本感染症学会総会・学術講演会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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