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タイトル: In Vivo Genetic Manipulation of Spermatogonial Stem Cells and Their Microenvironment by Adeno-Associated Viruses
著者: Watanabe, Satoshi  kyouindb  KAKEN_id
Kanatsu-Shinohara, Mito
Ogonuki, Narumi
Matoba, Shogo
Ogura, Atsuo
Shinohara, Takashi
著者名の別形: 渡邉, 哲史
篠原, 美都
越後貫, 成美
的場, 章悟
小倉, 淳郎
篠原, 隆司
キーワード: adeno-associated virus
blood-testis barrier
Sertoli cells
spermatogonia
spermatogenesis
発行日: 8-May-2018
出版者: Elsevier BV
誌名: Stem Cell Reports
巻: 10
号: 5
開始ページ: 1551
終了ページ: 1564
抄録: Adeno-associated virus (AAV) penetrates the blood-brain barrier, but it is unknown whether AAV penetrates other tight junctions. Genetic manipulation of testis has been hampered by the basement membrane of seminiferous tubules and the blood-testis barrier (BTB), which forms between Sertoli cells and divides the tubules into basal and adluminal compartments. Here, we demonstrate in vivo genetic manipulation of spermatogonial stem cells (SSCs) and their microenvironment via AAV1/9. AAV1/9 microinjected into the seminiferous tubules penetrated both the basement membrane and BTB, thereby transducing not only Sertoli cells and SSCs but also peritubular cells and Leydig cells. Moreover, when congenitally infertile KitlSl/KitlSl-d mouse testes with defective Sertoli cells received Kitl-expressing AAVs, spermatogenesis regenerated and offspring were produced. None of the offspring contained the AAV genome. Thus, AAV1/9 allows efficient germline and niche manipulation by penetrating the BTB and basement membrane, providing a promising strategy for the development of gene therapies for reproductive defects.
記述: セルトリ細胞への遺伝子導入による新規男性不妊治療法の開発 --ヒト不妊治療への応用に期待--. 京都大学プレスリリース. 2018-04-10.
著作権等: © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/2433/230498
DOI(出版社版): 10.1016/j.stemcr.2018.03.005
PubMed ID: 29628393
関連リンク: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/180406_1.html
出現コレクション:学術雑誌掲載論文等

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