Engelhardt J F, Allen E D, Wilson J M
Department of Internal Medicine, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11192-6. doi: 10.1073/pnas.88.24.11192.
A rational approach to the development of gene therapies for cystic fibrosis requires a better understanding of the cellular targets for gene transfer in the airway epithelium. We have used recombinant retroviruses to study the dynamics and lineage relationships of a regenerating rat tracheal epithelium. Primary cultures of tracheal epithelial cells were exposed to lacZ-transducing retroviruses and subsequently seeded into denuded trachea that were implanted into BALB/c (nu/nu) mice. The grafts developed a fully differentiated mucociliary epithelium containing large clones of lacZ-expressing cells with virtually all cell types represented within each clone. These data are most consistent with gene transfer into a putative progenitor cell that is capable of extensive self renewal and pleuripotent development. Vector-specific variation in transgene expression was noted in the various cell types.
一种合理开发囊性纤维化基因疗法的方法需要更好地了解气道上皮中基因转移的细胞靶点。我们使用重组逆转录病毒来研究再生大鼠气管上皮的动力学和谱系关系。将气管上皮细胞的原代培养物暴露于携带β-半乳糖苷酶（lacZ）的逆转录病毒中，随后接种到植入BALB/c（裸鼠）小鼠体内的去上皮气管中。移植组织发育出一个完全分化的黏液纤毛上皮，其中包含大量表达lacZ的细胞克隆，每个克隆中几乎代表了所有细胞类型。这些数据与基因转移到一个假定的祖细胞中最为一致，该祖细胞能够进行广泛的自我更新和多能发育。在各种细胞类型中观察到转基因表达的载体特异性差异。
