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In Vivo Myoblasts Tracking Using the Sodium Iodide Symporter Gene Expression in Dogs.
Molecular Therapy - Methods & Clinical Development ( IF 4.7 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.omtm.2019.12.011
Isabel Punzón 1 , David Mauduit 1 , Bryan Holvoet 2 , Jean-Laurent Thibaud 3 , Pauline de Fornel 3 , Christophe M Deroose 2 , Nicolas Blanchard-Gutton 1 , Jean-Thomas Vilquin 4 , Maurilio Sampaolesi 5 , Inès Barthélémy 1 , Stéphane Blot 1
Affiliation  

Stem cell-based therapies are a promising approach for the treatment of degenerative muscular diseases; however, clinical trials have shown inconclusive and even disappointing results so far. Noninvasive cell monitoring by medicine imaging could improve the understanding of the survival and biodistribution of cells following injection. In this study, we assessed the canine sodium iodide symporter (cNIS) reporter gene as an imaging tool to track by single-photon emission computed tomography (SPECT/CT) transduced canine myoblasts after intramuscular (IM) administrations in dogs. cNIS-expressing cells kept their myogenic capacities and showed strong 99 mTc-pertechnetate (99 mTcO4) uptake efficiency both in vitro and in vivo. cNIS expression allowed visualization of cells by SPECT/CT along time: 4 h, 48 h, 7 days, and 30 days after IM injection; biopsies collected 30 days post administration showed myofiber’s membranes expressing cNIS. This study demonstrates that NIS can be used as a reporter to track cells in vivo in the skeletal muscle of large animals. Our results set a proof of concept of the benefits NIS-tracking tool may bring to the already challenging cell-based therapies arena in myopathies and pave the way to a more efficient translation to the clinical setting from more accurate pre-clinical results.



中文翻译:

在犬中使用碘化钠共转运蛋白基因表达进行体内成肌细胞追踪。

基于干细胞的疗法是一种治疗退行性肌肉疾病的有前途的方法。然而,到目前为止,临床试验显示出不确定的甚至令人失望的结果。通过药物成像进行的非侵入性细胞监测可以改善对注射后细胞存活和生物分布的了解。在这项研究中,我们评估了犬肌肉注射(IM)后,犬碘化碘共转运体(cNIS)报告基因作为一种成像工具,以通过单光子发射计算机断层扫描(SPECT / CT)转导的犬成肌细胞进行跟踪。CNIS表达细胞保持它们的生肌能力和表现出很强的99米锝高锝酸盐(99米TCO 4 - )的吸收效率二者在体外体内。cNIS表达允许通过IMECT注射后4小时,48小时,7天和30天通过SPECT / CT观察细胞。给药后30天收集的活检表明肌纤维膜表达cNIS。这项研究表明,NIS可以用作报告基因,以追踪大型动物骨骼肌中的体内细胞。我们的结果为NIS追踪工具可能为肌病带来了挑战,已经为基于细胞的治疗领域带来了益处,并为从更准确的临床前结果更有效地转化为临床环境铺平了道路。

更新日期:2020-01-09
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