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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells
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Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells

机译：通过肌肉祖细胞全身递送人微营养不良蛋白到再生小鼠营养不良性肌肉

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Cell-based therapy for Duchenne muscular dystrophy patients and mdx mice has proven to be a safe but ineffective form of treatment. Recently, a group of cells called muscle side population (SP) cells have been isolated based on their ability to efflux the DNA-binding dye Hoechst. To understand the potential of skeletal muscle SP cells to serve as precursors for muscle, SP cells from the two mice strains mdx(5cv) and C57BL/6N were isolated, transduced, and transplanted. Under coculture conditions with myogenic cells, some cells within the SP cell population can give rise to early Pax7-positive satellite cells and other later stage myogenic cells. Transduced SP cells were transplanted via the tail vein and were shown to successfully deliver enhanced GFP and human microdystrophin to the skeletal muscle of nonirradiated mdx(5cv) mice, thus demonstrating their ability to travel through the capillaries and enter into damaged muscle. These results demonstrate that i.v. delivery of genes via SP cells is possible and that these SP cells are capable of recapitulating the myogenic lineage. Because this approach shows definitive engraftment by using autologous transplantation of noninjured recipients, our data may have substantial implications for therapy of muscular dystrophy. [References: 38]
机译：已经证明，针对杜兴氏肌营养不良症患者和mdx小鼠的基于细胞的疗法是一种安全但无效的疗法。近来，已经根据它们释放DNA结合染料Hoechst的能力，分离了一组称为肌肉侧群体（SP）细胞的细胞。为了了解骨骼肌SP细胞作为肌肉前体的潜力，分离，转导和移植了来自两种小鼠品系mdx（5cv）和C57BL / 6N的SP细胞。在与成肌细胞共培养的条件下，SP细胞群中的某些细胞可以产生早期Pax7阳性卫星细胞和其他后期成肌细胞。转导的SP细胞通过尾静脉移植，并被证明可以成功地将增强的GFP和人微营养不良蛋白递送至未辐照的mdx（5cv）小鼠的骨骼肌，从而证明了它们穿过毛细血管并进入受损肌肉的能力。这些结果证明了通过SP细胞递送基因是可能的，并且这些SP细胞能够概括肌原性谱系。由于这种方法通过使用未受伤受体的自体移植显示出了明确的植入，因此我们的数据可能对肌肉营养不良的治疗具有重要意义。 [参考：38]

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