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タイトル: | Bile Duct Regeneration with an Artificial Bile Duct Made of Gelatin Hydrogel Nonwoven Fabrics |
著者: | Uemoto, Yusuke Taura, Kojiro Nakamura, Daichi Xuefeng, Li Nam, Nguyen Hai Kimura, Yusuke Yoshino, Kenji Fuji, Hiroaki Yoh, Tomoaki https://orcid.org/0000-0001-6518-2077 (unconfirmed) Nishio, Takahiro Yamamoto, Gen Koyama, Yukinori Seo, Satoru Tsuruyama, Tatsuaki Iwaisako, Keiko Uemoto, Shinji Tabata, Yasuhiko Hatano, Etsuro |
著者名の別形: | 上本, 裕介 田浦, 康二朗 中村, 大地 木村, 有佑 吉野, 健史 藤, 浩明 楊, 知明 西尾, 太宏 山本, 玄 小山, 幸法 瀬尾, 智 鶴山, 竜昭 祝迫, 惠子 上本, 伸二 田畑, 泰彦 波多野, 悦朗 |
キーワード: | artificial bile duct gelatin regenerative medicine |
発行日: | Sep-2022 |
出版者: | Mary Ann Liebert Inc |
誌名: | Tissue Engineering Part A |
巻: | 28 |
号: | 17-18 |
開始ページ: | 737 |
終了ページ: | 748 |
抄録: | Although choledochojejunostomy is the standard technique for biliary reconstruction, there are various associated problems that need to be solved such as reflux cholangitis. Interposition with an artificial bile duct (ABD) to replace the resected bile duct maintains a physiological conduit for bile and may solve this problem. This study investigated the usefulness of an ABD made of gelatin hydrogel nonwoven fabric (GHNF). GHNF was prepared by the solution blow spinning method. The migration and activity of murine fibroblast L929 cells were examined in GHNF sheets. L929 cells migrated into GHNF sheets, where they proliferated and synthesized collagen, suggesting GHNF is a promising scaffold for bile duct regeneration. ABDs made of GHNF were implanted in place of resected bile duct segments in rats. The rats were killed at 2, 6, and 12 weeks postimplantation. The implantation site was histologically evaluated for bile duct regeneration. At postoperative 2 weeks, migrating cells were observed in the ABD pores. The implanted ABD was mostly degraded and replaced by collagen fibers at 6 weeks. Ki67-positive bile duct epithelial cells appeared within the implanted ABD. These were most abundant within the central part of the ABD after 6 weeks. The percentages of Ki67-positive cells were 31.7 ± 9.1% in the experimental group and 0.8 ± 0.6% in the sham operation group at 6 weeks (p < 0.05), indicating that mature biliary epithelial cells at the stump proliferated to regenerate the biliary epithelium. Biliary epithelial cells had almost completely covered the bile duct lumen at 12 weeks (epithelialization ratios: 10.4 ± 6.9% at 2 weeks, 93.1 ± 5.1% at 6 weeks, 99.2 ± 1.6% at 12 weeks). The regenerated epithelium was positive for the bile duct epithelium marker cytokeratin 19. Bile duct regeneration was accompanied by angiogenesis, as evidenced by the appearance of CD31-positive vascular structures. Capillaries were induced 2 weeks after implantation. The number of capillaries reached a maximum at 6 weeks and decreased to the same level as that of normal bile ducts at 12 weeks. These results showed that an ABD of GHNF contributed to successful bile duct regeneration in rats by facilitating the cell migration required for extracellular matrix synthesis, angiogenesis, and epithelialization. Impact Statement Development of an artificial bile duct (ABD) enables physiological biliary reconstruction and may solve clinical problems associated with choledochojejunostomy. In this study, we created ABDs with gelatin hydrogel nonwoven fabric and implanted them in place of resected bile duct in rats. We evaluated the process of bile duct regeneration as well as decomposition of the ABD and demonstrated successful regeneration of resected bile duct, highlighting the possibility of this novel biliary reconstruction method to replace choledochojejunostomy. |
著作権等: | This is the accepted version of the following article: [Yusuke Uemoto, Kojiro Taura, Daichi Nakamura, Li Xuefeng, Nguyen Hai Nam, Yusuke Kimura, Kenji Yoshino, Hiroaki Fuji, Tomoaki Yoh, Takahiro Nishio, Gen Yamamoto, Yukinori Koyama, Satoru Seo, Tatsuaki Tsuruyama, Keiko Iwaisako, Shinji Uemoto, Yasuhiko Tabata, and Etsuro Hatano. Tissue Engineering Part A 2022 28:17-18, 737-748], which has now been formally published in final form at Tissue Engineering Part A at https://doi.org/10.1089/ten.tea.2021.0209. This original submission version of the article may be used for non-commercial purposes in accordance with the Mary Ann Liebert, Inc., publishers’ self-archiving terms and conditions. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/276228 |
DOI(出版社版): | 10.1089/ten.TEA.2021.0209 |
PubMed ID: | 35383474 |
出現コレクション: | 学術雑誌掲載論文等 |
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