Shukla Shubha, Chaturvedi Rajnish Kumar, Seth Kavita, Roy Neeta Singh, Agrawal Ashok Kumar
Indian Institute of Toxicology Research, Lucknow, UP, India.
J Neurochem. 2009 Apr;109(2):436-51. doi: 10.1111/j.1471-4159.2009.05983.x. Epub 2009 Feb 13.
Transplantation of neural stem cell (NSC)-derived dopamine (DA) neurons is associated with low survival of cells, which could be due to limited striatal innervations and uneven distribution of graft because of its dense neuronal core, limited host-graft interaction, poor axonal outgrowth, lack of continuous neurotrophic factors supply, and an absence of cell adhesion molecules mediated appropriate developmental cues. Olfactory ensheathing cells (OEC) express a variety of growth factors and cell adhesion molecules and promote axonal regrowth and functional recovery in spinal cord injury in animal models and patients. In the present study, we explored the possibility to increase the survival, function, axonal outgrowth and striatal reinnervation of NSC by co-grafting with OEC in 6-OHDA lesioned parkinsonian rats. In the presence of OEC, significantly enhanced survival of NSC-derived DA neurons and axonal fiber outgrowth was evident in the striatum of NSC+OEC co-grafted rats at 24 weeks post-grafting as compared with NSC alone grafted rats. The increased survival of NSC and their striatal reinnervation was further manifested in the form of significant and substantial restitution of motor function and neurochemical recovery in the co-grafted group. Significant enhanced expression of p75NTR (from OEC) and tyrosine hydroxylase (TH) (from NSC) confirmed the co-localization and survival of both types of cells at the transplantation site in co-grafted rats. Co-grafting results co-related well with our in vitro studies, which suggest that OEC not only significantly increase survival, neurite outgrowth and DA release of NSC-derived DA neuron but also protect against 6-OHDA neurotoxicity in co-culture conditions. These results collectively suggest that OEC increase the survival and function of transplanted NSC in 6-OHDA lesioned parkinsonian rats.
神经干细胞（NSC）源性多巴胺（DA）神经元移植与细胞低存活率相关，这可能是由于纹状体神经支配有限、移植物因密集的神经元核心而分布不均、宿主 - 移植物相互作用有限、轴突生长不良、缺乏持续的神经营养因子供应以及缺乏细胞粘附分子介导的适当发育线索。嗅鞘细胞（OEC）表达多种生长因子和细胞粘附分子，并在动物模型和患者的脊髓损伤中促进轴突再生和功能恢复。在本研究中，我们探讨了在6 - 羟基多巴胺（6 - OHDA）损伤的帕金森病大鼠中通过与OEC共移植来提高NSC的存活率、功能、轴突生长和纹状体再支配的可能性。与单独移植NSC的大鼠相比，在OEC存在的情况下，NSC + OEC共移植大鼠纹状体中NSC源性DA神经元在移植后24周时存活率显著提高，轴突纤维生长明显。共移植组中NSC存活率的提高及其纹状体再支配进一步表现为运动功能的显著和实质性恢复以及神经化学恢复。p75神经营养因子受体（p75NTR，来自OEC）和酪氨酸羟化酶（TH，来自NSC）表达的显著增强证实了共移植大鼠移植部位两种类型细胞的共定位和存活。共移植结果与我们的体外研究结果高度相关，体外研究表明OEC不仅显著提高NSC源性DA神经元的存活率、神经突生长和DA释放，而且在共培养条件下还能保护细胞免受6 - OHDA神经毒性的影响。这些结果共同表明，OEC可提高6 - OHDA损伤的帕金森病大鼠中移植NSC的存活率和功能。
