ASCs优化微环境联合神经嵴干细胞修复脊髓损伤的实验研究

脊髓损伤后的病理改变集中体现在损伤局部微环境的变化，因此如何改善脊髓损伤后微环境是促进神经功能恢复的关键。目前研究发现，损伤后局部pro-BDNF表达量增加并通过P75NTR参与多项生理过程导致微环境失衡。激活态雪旺细胞（ASCs）大量分泌的BDNF可通过BDNF/pro-BDNF/p75NTR轴调节脊髓损伤后微环境，本课题拟通过观察ASCs分泌的BDNF抑制pro-BDNF对微环境中不同细胞系的负性作用，探索ASCs多途径优化损伤后微环境的效果及分子机制。神经嵴干细胞具有较强的向神经元分化的能力，是理想的“种子细胞”，因此本课题拟通过体外实验揭示ASCs促进神经嵴干细胞向神经元方向分化的内在规律，通过体内实验探索ASCs改善损伤微环境下联合神经嵴干细胞移植修复脊髓损伤的效果及作用机理。本课题在“优化微环境”下移植干细胞修复脊髓损伤，提高干细胞移植修复的效果，为脊髓损伤修复提供新的思路。

Pathological changes after spinal cord injury(SCI) primarily involves the deterioration of the microenvironment in the lesion site, therefore, the improvement of microenvironment after SCI is a key point to promote the recovery of neurologic function.It has been reported that the overexpression of pro-BDNF in the lesion site leads to imbalance of the microenvironment through the participance ofp75NTR in various physiological reactions.Activated Schwann cells (ASCs) accompanied with a large number of secretion of BDNF can effectively regulate microenvironmentby the BDNF/pro-BDNF/p75NTR axis, this subject proposed to explore the effect and molecular mechanism of the optimization to the microenvironmentby ASCs in multi-ways. Neural crest stem cells(NCSCs) are known as ideal seed cells for their strong ability to differentiate into neurons, thus the applicant proposed to figure out the inherent relationship of the differentiation from NCSCs towards neurons promoted by ASCs in vitro experimental observation,and the mechanism of repair after SCI by NCSCs transplantation under the microenvironment optimized by ASCs in rats is to be observed in vivo experimental observation . This subject aims to improve the effect of stem cell transplantation under optimized microenvironment, providing new schema for cell transplantation in the process of repair after SCI.