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利用聚赖氨酸修饰的腺病毒载体从小鼠骨髓基质细胞高效诱导成骨细胞分化

Efficient osteoblast differentiation from mouse bone marrow stromal cells with polylysin-modified adenovirus vectors.

作者信息

Tashiro Katsuhisa, Kondo Asami, Kawabata Kenji, Sakurai Haruna, Sakurai Fuminori, Yamanishi Koichi, Hayakawa Takao, Mizuguchi Hiroyuki

机构信息

Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.

出版信息

Biochem Biophys Res Commun. 2009 Jan 30;379(1):127-32. doi: 10.1016/j.bbrc.2008.12.055. Epub 2008 Dec 25.

Abstract

Bone marrow stromal cells (BMSCs) are expected to be a source for tissue regeneration because they can differentiate into multiple cell types. Establishment of efficient gene transfer systems for BMSCs is essential for their application to regenerative medicine. In this study, we compared the transduction efficiency in mouse primary BMSCs by using fiber-modified adenovirus (Ad) vectors, and demonstrated that AdK7, which harbors a polylysin (K7) peptide in the C-terminus of the fiber knob, could efficiently express a transgene in BMSCs. Notably, AdK7 robustly drove transgene expression in more than 90% of the BMSCs at 3,000 vector particles/cell. Furthermore, we showed that in vitro and in vivo osteogenic potential of BMSCs was dramatically promoted by the transduction of Runx2 gene using AdK7. These results indicate that this transduction system could be a powerful tool for therapeutic applications based on BMSCs.

摘要

骨髓基质细胞(BMSCs)有望成为组织再生的细胞来源,因为它们可以分化为多种细胞类型。建立高效的BMSCs基因转移系统对于其在再生医学中的应用至关重要。在本研究中,我们使用纤维修饰的腺病毒(Ad)载体比较了小鼠原代BMSCs的转导效率,并证明在纤维结的C末端含有聚赖氨酸(K7)肽的AdK7能够在BMSCs中高效表达转基因。值得注意的是,在每细胞3000个载体颗粒的条件下,AdK7能使超过90%的BMSCs强烈表达转基因。此外,我们还表明,使用AdK7转导Runx2基因可显著促进BMSCs在体外和体内的成骨潜能。这些结果表明,该转导系统可能是基于BMSCs的治疗应用的有力工具。

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