2021 Fiscal Year Final Research Report
Development of novel technology for intestinal epithelial replacement with urothelial organoids and its implementation in bladder augmentation
Project/Area Number |
20K21637
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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Research Institution | Juntendo University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
松本 有加 順天堂大学, 医学部, 助教 (50813672)
中村 哲也 順天堂大学, 大学院医学研究科, 特任教授 (70265809)
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Project Period (FY) |
2020-07-30 – 2022-03-31
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Keywords | 神経因性膀胱 / 膀胱拡大術 / 悪性腫瘍 / 膀胱上皮 / 分化制御機構 / オルガノイド / fibroblast growth factor / 腸上皮置換 |
Outline of Final Research Achievements |
By modifying a method described previously, we have developed in this study an organoid culture system of the murine bladder urothelium. We then aimed to characterize the differentiation/proliferation status of the organoid cells, and also transplant them onto the colon tissue of recipients’ mice. We observed that gene expression patterns of undifferentiated cell types in the bladder urothelium were dominantly preserved in organoids. Further, we found that different members of fibroblast growth factor (FGF) protein family possess distinctive effects on induction of urothelial differentiation. We also successfully engrafted the cultured bladder organoids onto murine proximal colon by using an epithelial replacement technique that we have developed, and carried out histological analyses of the graft tissue.
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Free Research Field |
小児外科、小児泌尿生殖器外科、新生児外科、神経因性膀胱
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Academic Significance and Societal Importance of the Research Achievements |
消化管を利用した膀胱拡大術の術後長期合併症として、腸粘膜と膀胱組織の混在に起因する膀胱内結石や悪性腫瘍の発生が大きな問題となっており、新規治療開発が切望されている。本研究では、マウス結腸上皮を安全に剥離し、独自に培養確立した正常マウス膀胱オルガノイドを移植することで膀胱上皮化ハイブリッド結腸作成の技術基盤を築いた。本研究成果と今後の更なる進展により、腸粘膜の存在に由来する合併症リスクを緩和させるための新規膀胱拡大術へと応用させる可能性がある。
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