Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells
Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells
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DOI：
10.1073/pnas.0400373101
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发表时间：
2004-03-09
影响因子：
11.1
通讯作者：
Kunkel, LM
中科院分区：
文献类型：
--
作者：
Bachrach, E;Li, S;Kunkel, LM
对杜氏肌营养不良症患者和mdx小鼠的细胞治疗已被证明是一种安全但无效的治疗形式。最近，一组称为肌侧群（SP）细胞的细胞已经被分离出来，基于它们流出DNA结合染料Hoechst的能力。为了了解骨骼肌SP细胞作为肌肉前体的潜力，从两个小鼠品系mdx（5cv）和C57 BL/6 N分离SP细胞，转导并移植。在与肌源性细胞共培养的条件下，SP细胞群中的一些细胞可以产生早期Pax 7阳性卫星细胞和其他晚期肌源性细胞。转导的SP细胞通过尾静脉移植，并成功地将增强的GFP和人微肌营养不良蛋白递送到未照射的mdx（5cv）小鼠的骨骼肌，从而证明它们能够穿过毛细血管并进入受损的肌肉。这些结果表明，通过SP细胞静脉内递送基因是可能的，并且这些SP细胞能够重现肌源性谱系。由于这种方法通过使用非损伤受体的自体移植显示了明确的植入，我们的数据可能对肌营养不良症的治疗有重大意义。
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.