Regeneration of hypoplastic lung with congenital diaphragmatic hernia using by umbilical cord mesenchymal stem cell sheet

• Project/Area Number: 15K15642
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatric surgery
• Research Institution: University of Tsukuba
• Principal Investigator: Shinkai Toko 筑波大学, 医学医療系, 講師 (80301612)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 再生医療 / 臍帯由来間葉系幹細胞 / 横隔膜ヘルニア / 肺低形成 / 臍帯間葉系幹細胞 / 先天性横隔膜ヘルニア / 肺高血圧 / 臍帯幹細胞 / 幹細胞シート / 細胞シート

Outline of Final Research Achievements

We observed the differentiation induction of fetal rat lung by co-culture with umbilical cord-derived mesenchymal stem cells (UC-WJSCs) and fetal rat lung which suitable for observation. We compared the usefulness of UC-WJSCs by the difference between Lung bud increase rate and expression of mRNA involved in fetal lung growth. The lung bud increment was significantly high in the co-culture group with UC-WJSCs. In addition, the mRNA expressions of VEGF, BMP-4 and TTF-1, which are factors of lung angiogenesis and lung branching morphogenesis, were significantly higher in the co-culture group with UC-WJSCs. However, there was no significant difference between the two groups in the expression of Shh.

Academic Significance and Societal Importance of the Research Achievements

本研究は小児の難治性疾患に対する再生医療の可能性を示す基礎実験となったと考えられる。また、出産後に廃棄される臍帯を再生医療の原資に用いる可能性を示せたことも本研究の学術的、社会的な意義は大きいものと考える。

Research Products

• [Presentation] 臍帯由来間葉系幹細胞を用いたラット胎児肺の分化誘導に関する展望と課題 (2018)
  • Author(s): 新開統子、増本幸二、川見明央、田中 尚、相吉 翼、佐々木理人、石川未来、千葉史子、小野健太郎、川上 肇、五藤 周、瓜田泰久、高安 肇
  • Organizer: 第55回日本小児外科学会総会
• [Presentation] Effects of umbilical cord mesenchymal stem cells on the vascular growth of fetal lung explants (2016)
  • Author(s): Toko Shinkai, Kouki, Masumoto, Xue Lian, Kouki Hagiwara, Chikashi Gotoh, Yasuhisa Urita, Naoya Sakamoto, Fumiko Chiba, Hajime Takayasu, Hideaki Tanaka
  • Organizer: The24th Congress of the Asian Association of Pediatric Surgeons
  • Place of Presentation: ヒルトン福岡シーホーク、福岡市
  • Year and Date: 2016-05-24
  • Int'l Joint Research