Inserm U955-E10, IMRB, Université Paris Est Créteil. Ecole nationale vétérinaire d'Alfort, 94700, Maisons-Alfort, France.
MICEN-Vet, 94000, Créteil, France.
Sci Rep. 2020 Jun 30;10(1):10681. doi: 10.1038/s41598-020-66388-w.
One of the main challenges in cell therapy for muscle diseases is to efficiently target the muscle. To address this issue and achieve better understanding of in vivo cell fate, we evaluated the relevance of a non-invasive cell tracking method in the Golden Retriever Muscular Dystrophy (GRMD) model, a well-recognised model of Duchenne Muscular Dystrophy (DMD). Mesoangioblasts were directly labelled with In-oxine, and injected through one of the femoral arteries. The scintigraphy images obtained provided the first quantitative mapping of the immediate biodistribution of mesoangioblasts in a large animal model of DMD. The results revealed that cells were trapped by the first capillary filters: the injected limb and the lung. During the days following injection, radioactivity was redistributed to the liver. In vitro studies, performed with the same cells prepared for injecting the animal, revealed prominent cell death and In release. In vivo, cell death resulted in In release into the vasculature that was taken up by the liver, resulting in a non-specific and non-cell-bound radioactive signal. Indirect labelling methods would be an attractive alternative to track cells on the mid- and long-term.
肌肉疾病细胞治疗的主要挑战之一是如何有效地将细胞靶向到肌肉。为了解决这个问题,并更好地了解体内细胞的命运,我们评估了一种非侵入性细胞示踪方法在 Golden Retriever 肌肉营养不良症(GRMD)模型中的相关性,该模型是一种公认的杜氏肌肉营养不良症(DMD)模型。中胚层成肌细胞用 In-oxine 直接标记,并通过股动脉之一注入。获得的闪烁扫描图像首次提供了 DMD 大型动物模型中中胚层成肌细胞即时生物分布的定量图谱。结果表明,细胞被第一个毛细血管过滤器捕获:注射的肢体和肺。在注射后的几天内,放射性物质重新分布到肝脏。体外研究使用与用于注射动物的相同细胞进行,显示出明显的细胞死亡和 In 释放。在体内,细胞死亡导致 In 释放到血管中,被肝脏摄取,导致非特异性和非细胞结合的放射性信号。间接标记方法将是一种有吸引力的替代方法,可以在中期和长期跟踪细胞。