2019 Fiscal Year Final Research Report
Evaluation of pharmaceutical HO-1 induction and mesenchymal stem cell combination therapy in meconium peritonitis mouse model
| Project/Area Number |
18K15710
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | 胎便性腹膜炎 / 炎症性疾患 / ヒト胎便 / 早産児マウス敗血症モデル / モデルマウス / 糞便懸濁液 / HO-1 / 間葉系幹細胞 |
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| Outline of Final Research Achievements |
Background: Meconium peritonitis is caused by leakage of meconium into the fetal peritoneal cavity due to intestinal perforation. Objective: To generate a neonatal mouse model of meconium peritonitis via IP administration of human meconium suspension or “slurry” (MS) by applying the CS methodology. Methods: Fresh meconium was suspended in PBS to 500 mg/mL. 200 μL of MS (meconium) or PBS (control) was administered IP to 4d-old wild-type FVB mice pups. Body weight and survivals was monitored. Results: Administration of MS resulted in significant decreases in weight gain and survival (0.8±7.5% (n=26), and 58.8% (n=34), respectively) compared with PBS controls (18.6±4.8% (n=10) and 100% (n=10), respectively). Conclusions: IP administration of MS resulted in significant mortality and weight loss to 4d-old newborn pups, and affects blood gasses and electrolytes. Therefore, we conclude that this MS model can be used to study the pathophysiology and treatment of meconium peritonitis.
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| Free Research Field |
胎児・新生児医学
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| Academic Significance and Societal Importance of the Research Achievements |
胎便性腹膜炎は、周産期の難治性疾患であり、胎生期の腸管穿孔により無菌性の胎便が腹腔内に漏出して生じる化学性腹膜炎と定義される。一方、その病態を反映する動物モデルが無く、有効な治療法もない。
本研究では、「胎便性腹膜炎の病態解明のための疾患モデル動物は確立できるか？」という学術的問いに解答するために、申請者の新生児モデルマウス作成技術を駆使し、胎便性腹膜炎モデルマウスを作製・解析し、新規治療法開発のための基盤を確立した。本モデルマウスの確立により、今後、薬物的ヘムオキシゲナーゼ-1誘導、間葉系幹細胞投与などの新規治療法の有効性の検討が可能となり、本研究成果の学術的意義は大きいと考えている。
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