Bachrach Estanislao, Li Sheng, Perez Antonio L, Schienda Jaclyn, Liadaki Kalliopi, Volinski Jay, Flint Alan, Chamberlain Jeffrey, Kunkel Louis M
Genetics Division, Howard Hughes Medical Institute, and Children's Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3581-6. doi: 10.1073/pnas.0400373101. Epub 2004 Mar 1.
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.
对于杜氏肌营养不良症患者和mdx小鼠而言，基于细胞的疗法已被证明是一种安全但无效的治疗方式。最近，一组被称为肌肉侧群（SP）细胞的细胞已根据其排出DNA结合染料Hoechst的能力被分离出来。为了了解骨骼肌SP细胞作为肌肉前体细胞的潜力，从mdx(5cv)和C57BL/6N这两种小鼠品系中分离、转导并移植了SP细胞。在与成肌细胞共培养的条件下，SP细胞群体中的一些细胞可产生早期Pax7阳性卫星细胞和其他后期成肌细胞。转导后的SP细胞通过尾静脉进行移植，并被证明能成功地将增强型绿色荧光蛋白和人微肌营养不良蛋白递送至未受辐射的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肌肉。这些结果表明，通过SP细胞进行静脉内基因递送是可行的，并且这些SP细胞能够重现成肌谱系。由于这种方法通过对未受伤受体进行自体移植显示出明确的植入，我们的数据可能对肌营养不良症的治疗具有重大意义。
