Regeneration of functional alveoli by adult human SOX9(+) airway basal cell transplantation.
Regeneration of functional alveoli by adult human SOX9(+) airway basal cell transplantation.
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成人SOX9( )气道基底细胞移植再生功能性肺泡
DOI：
10.1007/s13238-018-0506-y
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发表时间：
2018-03
期刊：
影响因子：
21.1
通讯作者：
Zuo W
中科院分区：
文献类型：
--
作者：
Ma Q;Ma Y;Dai X;Ren T;Fu Y;Liu W;Han Y;Wu Y;Cheng Y;Zhang T;Zuo W
对支气管和肺泡的不可逆破坏可导致多种无法治愈的肺部疾病。鉴定具有再生能力的肺干/祖细胞并利用它们重建功能组织是逆转损伤和治愈此类疾病的最大希望之一。本研究表明，位于气道上皮rugae的罕见SOX9+基底细胞（BCs）群体可以再生成人肺。人SOX9+ bc可以很容易地通过支气管镜刷洗分离出来，并在无饲料条件下无限扩增。扩增的人SOX9+ BCs移植到损伤小鼠肺后可产生肺泡上皮和细支气管上皮，重建气血交换系统，改善受体肺功能。吡非尼酮调控肺微环境抑制TGF-β信号可进一步提高移植效率。此外，我们在2例支气管扩张患者中进行了首次自体SOX9+ bc移植临床试验。细胞移植后3-12个月观察到肺组织修复和肺功能增强。总之，我们目前的工作表明，组织特异性干细胞/祖细胞原位移植可以重建功能性成人肺结构，这在不久的将来可以转化为成熟的再生治疗策略。本文的在线版本（10.1007/s13238-018-0506-y）包含补充内容，仅供授权用户使用。
Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9+ basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9+ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9+ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient’s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9+ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3–12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future. The online version of this article (10.1007/s13238-018-0506-y) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG
通讯作者：
Crystal RG
影响因子：
5
作者：
Chilosi, M;Poletti, V;Doglioni, C
通讯作者：
Doglioni, C
DOI：
10.1073/pnas.1311847110
发表时间：
2013-11-19
影响因子：
11.1
作者：
Rockich, Briana E.;Hrycaj, Steven M.;Spence, Jason R.
通讯作者：
Spence, Jason R.
影响因子：
1.5
作者：
Perl, AKT;Kist, R;Whitsett, JA
通讯作者：
Whitsett, JA
影响因子：
82.9
作者：
Ott, Harald C.;Clippinger, Ben;Vacanti, Joseph P.
通讯作者：
Vacanti, Joseph P.