Differentiated Mesenchymal Stem Cells for Sciatic Nerve Injury
Differentiated Mesenchymal Stem Cells for Sciatic Nerve Injury
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DOI：
10.1007/s12015-010-9227-1
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发表时间：
2011-09-01
影响因子：
4.8
通讯作者：
Offen, Daniel
中科院分区：
文献类型：
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作者：
Dadon-Nachum, Michal;Sadan, Ofer;Offen, Daniel
坐骨神经损伤是常见的，并可能导致神经功能缺损。以往的研究表明，神经营养因子（NTFs），天然存在的蛋白质，支持神经元的发育和存活，保存和保护受损的运动神经元在受伤的坐骨神经的管理。我们已经成功地将骨髓间充质干细胞转化为产生和分泌NTF的星形胶质细胞样细胞（NTF+细胞）。这些细胞表现出典型的星形胶质细胞形态，表达特征性星形胶质细胞标志物并分泌高水平的NTFs。我们已经证明，这些细胞和它们的条件培养基可以在培养和神经退行性疾病的动物模型中保护神经元。在目前的研究中，我们研究了NTF+细胞是否能够在大鼠坐骨神经损伤模型中拯救运动神经元，其中右后肢坐骨神经被压碎。将NTF+细胞、MSC或PBS移植到大鼠的病变部位。在注射NTF+细胞的大鼠中，运动功能显著保留。此外，NTF+细胞显着抑制神经肌肉接头的变性和保存有髓运动轴突。我们的研究结果表明，自体治疗方法可以减轻坐骨神经损伤的迹象，并可能其他神经系统疾病。
Sciatic nerve injury is common and may cause neurological deficits. Previous studies showed that administration of neurotrophic factors (NTFs), naturally occurring proteins that support the development and survival of neurons, preserved and protected damaged motor neuron in the injured sciatic nerve. We have been successful in converting bone marrow-derived mesenchymal stem cells into astrocyte-like cells that produce and secrete NTFs (NTF+ cells). These cells demonstrate typical astrocyte morphology, express characteristic astrocyte markers and secrete high levels of NTFs. We have already shown that these cells and their conditioned media can protect neurons in culture and in animal models of neurodegenerative diseases. In the current study we examined whether NTF+ cells are capable of rescuing motor neurons in a rat sciatic nerve injury model, where the right hind limb sciatic nerve was crushed. Rats were transplanted with NTF+ cells, MSCs or PBS into the lesion site. In rats injected with the NTF+ cells motor function was markedly preserved. Moreover, NTF+ cells significantly inhibited the degeneration of the neuromuscular junctions and preserved the myelinated motor axons. Our findings suggest that autologous therapeutic approach can alleviate signs of sciatic nerve injury and probably other neurological disorders.