2022 Fiscal Year Final Research Report
Development of novel embryonic stem cell-based cartilage for pediatric airway stenosis
Project/Area Number |
19H03720
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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Research Institution | Keio University |
Principal Investigator |
FUCHIMOTO Yasushi 慶應義塾大学, 医学部(信濃町), 講師(非常勤) (40219077)
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Co-Investigator(Kenkyū-buntansha) |
黒田 達夫 慶應義塾大学, 医学部(信濃町), 教授 (60170130)
梅澤 明弘 国立研究開発法人国立成育医療研究センター, 再生医療センター, 再生医療センター長 (70213486)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 先天性声門下狭窄症 / 先天性気管狭窄症 / ES細胞 / 軟骨組織 / 医療的ケア児 |
Outline of Final Research Achievements |
Successfully generated 15x15mm size cartilage tissue from human ES cells by transplantation into immunocompromised mice. There were no problems in safety evaluation of tumorigenicity and infectivity. In the evaluation of the functionality of human ES-derived cartilage tissue as trachea, patch transplantation into nude rat trachea showed regenerative fusion of rat cartilage and human ES-derived cartilage in 3 months. In rabbits, the trachea was fragile and died of respiratory failure due to procedural problems. In the case of patch transplantation into pig trachea, all pigs did not show respiratory failure at 1 month, but 1) cartilage was lost due to rejection in untreated pigs, 2) the lumen was narrowed in immunocompromised pigs, and prominent mononuclear cell infiltration and thickening of granulation tissue were observed due to rejection, and 3) In high-pressure decellularized human ES-derived cartilage, rejection was mild compared to 2).
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Free Research Field |
小児外科、小児呼吸器外科、再生医療
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Academic Significance and Societal Importance of the Research Achievements |
先天性声門下狭窄症や先天性気管狭窄症、ならびに長期気管切開後に生じる小児気道狭窄患児の治療は難渋することが多い。 本研究では気道狭窄の患児ならびに気管孔閉鎖困難な患児に対してES細胞を細胞ソースとする軟骨パッチグラフトにより気道内腔を拡げることにより挿管管理・気管切開からの離脱を期待している。本研究の成果から乳幼児の気管径に応用可能なヒトES由来軟骨を作成することができた。また同種免疫原性の問題があるが、気管壁の機能を持ち得ることが示された。更に再生軟骨同士の癒合もみられ狭窄予防ならびに患児の成長に伴う気管の成長も期待できる可能性も示された。
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