Nerve growth factor improves the muscle regeneration capacity of muscle stem cells in dystrophic muscle
Nerve growth factor improves the muscle regeneration capacity of muscle stem cells in dystrophic muscle
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DOI：
10.1089/hum.2006.17.180
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发表时间：
2006-02-01
影响因子：
4.2
通讯作者：
Huard, J
中科院分区：
文献类型：
--
作者：
Lavasani, M;Lu, AP;Huard, J
研究人员已经尝试使用基因和细胞为基础的疗法来恢复肌营养不良蛋白，减轻由杜氏肌营养不良症（DMD）引起的肌肉无力。我们的研究小组已经从小鼠的出生后骨骼肌中分离出了肌肉来源的干细胞（MDSCs）群体。与卫星细胞相比，MDSCs在营养不良的mdx肌肉中表现出更好的移植能力，我们将其归因于它们能够经历长期增殖、自我更新和多能分化，包括向内皮细胞和神经元谱系的分化。在这里，我们测试了神经生长因子（NGF）的使用是否能提高MDSCs的移植效率。我们使用了两种体外刺激NGF的方法：用CL-NGF载体逆转录病毒转导MDSCs和用NGF蛋白直接刺激MDSCs。两种NGF处理方法均未改变MDSCs的标记谱或增殖行为，但直接用NGF蛋白刺激可显著降低细胞的体外分化能力。NGF刺激也显著提高mdx小鼠营养不良肌肉内MDSCs的移植效率，导致大量肌营养不良蛋白阳性肌纤维再生。这些发现强调了神经生长因子作为一种调节分子的重要性，对其的研究将拓宽我们对其在肌肉来源细胞的骨骼肌再生和修复中的生物学作用的理解。
Researchers have attempted to use gene- and cell-based therapies to restore dystrophin and alleviate the muscle weakness that results from Duchenne muscular dystrophy (DMD). Our research group has isolated populations of muscle-derived stem cells (MDSCs) from the postnatal skeletal muscle of mice. In comparison with satellite cells, MDSCs display an improved transplantation capacity in dystrophic mdx muscle that we attribute to their ability to undergo long-term proliferation, self-renewal, and multipotent differentiation, including differentiation toward endothelial and neuronal lineages. Here we tested whether the use of nerve growth factor (NGF) improves the transplantation efficiency of MDSCs. We used two methods of in vitro NGF stimulation: retroviral transduction of MDSCs with a CL-NGF vector and direct stimulation of MDSCs with NGF protein. Neither method of NGF treatment changed the marker profile or proliferation behavior of the MDSCs, but direct stimulation with NGF protein significantly reduced the in vitro differentiation ability of the cells. NGF stimulation also significantly enhanced the engraftment efficiency of MDSCs transplanted within the dystrophic muscle of mdx mice, resulting in the regeneration of numerous dystrophin-positive muscle fibers. These findings highlight the importance of NGF as a modulatory molecule, the study of which will broaden our understanding of its biologic role in the regeneration and repair of skeletal muscle by muscle-derived cells.