Donofrio Gaetano, Capocefalo Antonio, Franceschi Valentina, Morini Giorgio, Del Bue Maurizio, Conti Virna, Cavirani Sandro, Grolli Stefano
Dipartimento di Salute Animale, Sezione di Malattie Infettive, Facoltà di Medicina Veterinaria, via del Taglio 10, 43100 Parma, Italy.
BMC Cell Biol. 2010 Sep 23;11:73. doi: 10.1186/1471-2121-11-73.
Adipose-Derived Stromal Cells have been shown to have multiple lineage differentiation properties and to be suitable for tissues regeneration in many degenerative processes. Their use has been proposed for the therapy of joint diseases and tendon injuries in the horse. In the present report the genetic manipulation of Equine Adipose-Derived Stromal Cells has been investigated.
Equine Adipose-Derived Stromal Cells were successfully virally transduced as well as transiently and stably transfected with appropriate parameters, without detrimental effect on their differentiation properties. Moreover, green fluorescent protein alone, fused to neo gene, or co-expressed as bi-cistronic reporter constructs, driven by viral and house-keeping gene promoters, were tested. The better expressed cassette was employed to stably transfect Adipose-Derived Stromal Cells for cell therapy purposes. Stably transfected Equine Adipose-Derived Stromal Cells with a heterologous secreted viral antigen were able to immunize horses upon injection into the lateral wall of the neck.
This study provides the methods to successfully transgenize Adipose-Derived Stromal Cells both by lentiviral vector and by transfection using optimized constructs with suitable promoters and reporter genes. In conclusion these findings provide a working platform for the delivery of potentially therapeutic proteins to the site of cells injection via transgenized Equine Adipose-Derived Stromal Cells.
脂肪来源的基质细胞已被证明具有多种谱系分化特性,适用于许多退行性过程中的组织再生。有人提议将其用于治疗马的关节疾病和肌腱损伤。在本报告中,对马脂肪来源的基质细胞的基因操作进行了研究。
马脂肪来源的基质细胞成功地被病毒转导,并以适当的参数进行了瞬时和稳定转染,且对其分化特性没有不利影响。此外,还测试了单独的绿色荧光蛋白,其与新霉素基因融合,或作为由病毒和管家基因启动子驱动的双顺反子报告构建体共表达。使用表达效果更好的盒式结构对脂肪来源的基质细胞进行稳定转染,用于细胞治疗目的。用异源分泌病毒抗原稳定转染的马脂肪来源的基质细胞注射到颈部侧壁后能够使马产生免疫反应。
本研究提供了通过慢病毒载体以及使用具有合适启动子和报告基因的优化构建体进行转染来成功使脂肪来源的基质细胞转基因的方法。总之,这些发现为通过转基因的马脂肪来源的基质细胞将潜在治疗性蛋白递送至细胞注射部位提供了一个工作平台。