摘要
利用慢病毒(LV)“体外”局部基因治疗载体过表达骨形成蛋白-2(BMP-2)是提高动物模型的骨愈合的一种有效方法。在这里,我们评估了两种不同的“体外”实验方法,使用的是“同一天”的大鼠骨髓细胞(SDRBMCs)或体外培养的大鼠骨髓细胞(C-RBMCs),基于两步激活系统过表达GFP(LV-TSTA-EGFP),两者均通过慢病毒转导,观察转染细胞的生存和这种方法的安全性。转导的细胞植入同系大鼠股骨缺损处。术后4、14、28及56天处死动物(n = 5只/每组)。病毒的复制在SD-RBMC组缺损部位进行检测和逐渐下降8w(相比4d减少了5 log)。在SD-RBMC动物中,有在2w、4w的病毒拷贝数下降2-4 log,但在8w有相对增加(约100倍)在4缺损部位的病毒载体的数量(5)动物相比之前的时间点。对于这两种基因转移的方法,组织分布的模式是非特异性的,并且在任何一组中都没有组织学异常。总之,我们证明了LV-TSTA转导的细胞至少在缺损部位保持56天,虽然数量随时间的延长而下降。在内部器官的病毒复制中没有一致的结果,用于人类的这种策略的相关发展是令人鼓舞的。
关键词: 病毒载体分布,骨修复,体外基因治疗及安全性。
Current Gene Therapy
Title:Biodistribution of LV-TSTA Transduced Rat Bone Marrow Cells Used for “Ex-vivo” Regional Gene Therapy for Bone Repair
Volume: 15 Issue: 5
Author(s): Farhang Alaee, Cynthia Bartholomae, Osamu Sugiyama, Mandeep S. Virk, Hicham Drissi, Qian Wu, Manfred Schmidt and Jay R. Lieberman
Affiliation:
关键词: 病毒载体分布,骨修复,体外基因治疗及安全性。
摘要: “Ex vivo” regional gene therapy using lentiviral (LV) vectors to over-express bone morphogenetic protein 2 (BMP-2) is an effective way to enhance bone healing in animal models. Here, we evaluated two different “ex vivo” approaches using either “same day” rat bone marrow cells (SDRBMCs) or cultured rat bone marrow cells (C-RBMCs), both transduced with a LV based two-step transcriptional activation system overexpressing GFP (LV-TSTA-EGFP), to assess the fate of the transduced cells and the safety of this approach. The transduced cells were implanted in femoral defects of syngeneic rats. Animals were sacrificed at 4, 14, 28 and 56 days after surgery (n=5 per group). Viral copies were detectable in the defect site of SD-RBMC group and gradually declined at 8w (5 log decrease compared to 4d). In the C-RBMC animals, there was a 2-4 log decline in the viral copy numbers at 2w and 4w, but at 8w there was a relative rise (about 100 fold) in the number of the viral vectors in the defect site of 4 (out of 5) animals compared to the previous time points. For both gene transfer approaches, the pattern of tissue distribution was non-specific and no histological abnormalities were noted in either group. In summary, we demonstrated that the LV-TSTA transduced cells remain in the defect site for at least 56 days, though the numbers decreased over time. There were no consistent findings of viral copies in internal organs which is encouraging with respect to the development of this strategy for use in humans.
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Alaee Farhang, Bartholomae Cynthia, Sugiyama Osamu, Virk S. Mandeep, Drissi Hicham, Wu Qian, Schmidt Manfred and Lieberman R. Jay, Biodistribution of LV-TSTA Transduced Rat Bone Marrow Cells Used for “Ex-vivo” Regional Gene Therapy for Bone Repair, Current Gene Therapy 2015; 15 (5) . https://dx.doi.org/10.2174/1566523215666150812120229
DOI https://dx.doi.org/10.2174/1566523215666150812120229 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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