Analysis of adeno-associated virus progenitor cell transduction in mouse lung.
Analysis of adeno-associated virus progenitor cell transduction in mouse lung.
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DOI：
10.1038/mt.2008.248
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发表时间：
2009-02
影响因子：
12.4
通讯作者：
Engelhardt, John F.
中科院分区：
文献类型：
--
作者：
Liu, Xiaoming;Luo, Meihui;Guo, Chenhong;Yan, Ziying;Wang, Yujiong;Lei-Butters, Diana C. M.;Engelhardt, John F.
虽然重组腺相关病毒（rAAV）已被广泛用于肺基因治疗方法，它仍然不清楚在何种程度上常用的AAV血清型在肺中的成体祖细胞。在这项研究中，我们评估了寿命和增殖能力的rAAV 1，2和5转导的气道细胞在小鼠肺，使用LacZ-CRE报告基因转基因模型和Cre表达rAAV。在该模型中，CRE重组酶的表达导致转导细胞及其后代用LacZ进行永久遗传标记。为了研究rAAV转导的细胞是否包括气道祖细胞，我们用萘损伤rAAV感染小鼠的气道，同时用5-溴脱氧尿苷（BrdU）标记以鉴定进入细胞周期并保留标记的慢循环祖细胞/干细胞。rAAV 5和rAAV 1载体都能够转导长寿命Clara细胞和肺泡II型（ATII）细胞的子集，这些细胞保留核苷酸标记并在肺损伤后增殖。重要的是，rAAV 1和5似乎在培养物中和肺损伤后的体内都优先选择具有克隆扩增能力的气道上皮祖细胞。这些研究表明，rAAV可能是一个有用的载体，基因靶向气道干/祖细胞。
Although recombinant adeno-associated virus (rAAV) has been widely used in lung gene therapy approaches, it remains unclear to what extent commonly used AAV serotypes transduce adult progenitors in the lung. In this study, we evaluated the life span and proliferative capacity of rAAV1-, 2-, and 5-transduced airway cells in mouse lung, using a LacZ-CRE reporter transgenic model and Cre-expressing rAAV. In this model, the expression of CRE recombinase led to permanent genetic marking of transduced cells and their descendants with LacZ. To investigate whether the rAAV-transduced cells included airway progenitors, we injured the airways of rAAV-infected mice with Naphthalene, while simultaneously labeling with 5-bromodeoxyuridine (BrdU) to identify slow-cycling progenitor/stem cells that entered the cell cycle and retained label. Both rAAV5 and rAAV1 vectors were capable of transducing a subset of long-lived Clara cells and alveolar type II (ATII) cells that retained nucleotide label and proliferated following lung injury. Importantly, rAAV1 and 5 appeared to preferentially transduce conducting airway epithelial progenitors that had the capacity to clonally expand, both in culture and in vivo following lung injury. These studies suggest that rAAV may be a useful vector for gene targeting of airway stem/progenitor cells.
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影响因子：
5.4
作者：
Hansen, J;Qing, K;Srivastava, A
通讯作者：
Srivastava, A
影响因子：
3.5
作者：
Chng, Keefe;Larsen, Stephen R.;Rasko, John E. J.
通讯作者：
Rasko, John E. J.
影响因子：
12.4
作者：
Liu, YH;Okada, T;Ozawa, K
通讯作者：
Ozawa, K
影响因子：
5.1
作者：
Liu, X.;Luo, M.;Engelhardt, J. F.
通讯作者：
Engelhardt, J. F.
影响因子：
11.2
作者：
Shi, J;Zheng, DX;Xu, RA
通讯作者：
Xu, RA