Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration

• 資料種別: 博士論文
• ISSN: 1757-6512
• タイトル: Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration
• 巻次・部編番号: 11
• 著者・編者: Kawakita, Naoya; Toba, Hiroaki; Miyoshi, Keiko; Sakamoto, Shinichi; Matsumoto, Daisuke; Takashima, Mika; Aoyama, Mariko; Inoue, Seiya; Morimoto, Masami; Nishino, Takeshi; Takizawa, Hiromitsu; Tangoku, Akira
• 著者標目: Kawakita, Naoya; Toba, Hiroaki; Miyoshi, Keiko; Sakamoto, Shinichi; Matsumoto, Daisuke; Takashima, Mika; Aoyama, Mariko; Inoue, Seiya; Morimoto, Masami; Nishino, Takeshi; Takizawa, Hiromitsu; Tangoku, Akira
• 出版事項: BioMed Central|Springer Nature
• 出版年月日等: 2020-10-02
• 出版年（W3CDTF）: 2020-10-02
• 並列タイトル等: マウスiPS細胞由来の気管支肺胞幹細胞は末梢気道上皮再生を促進する
• タイトル（掲載誌）: Stem Cell Research & Therapy
• 授与機関名: 徳島大学
• 授与年月日: 2020-11-26
• 授与年月日（W3CDTF）: 2020-11-26
• 報告番号: 甲第3466号
• 学位: 博士（医学）
• 博論授与番号: 甲第3466号
• 本文の言語コード: eng
• 件名標目: stem cell; induced pluripotent stem cells; lung regeneration; bronchioloalveolar stem cell; Stem cell transplantation; Progenitor cells; Tissue regeneration
• 対象利用者: 一般
• 一般注記: Background: Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles.Methods: BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated.Results: Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs.Conclusions: Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.
• DOI: info:doi/10.1186/s13287-020-01946-7; https://doi.org/info:doi/10.1186/s13287-020-01946-7
• 国立国会図書館永続的識別子: info:ndljp/pid/11630048; https://dl.ndl.go.jp/pid/11630048
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2021-01-30T08:56:55+09:00
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/115515
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp