先天性脊柱裂是常见的先天畸形之一，目前对于患儿神经功能的损伤尚无良好治疗方法。前期我们建立了胎鼠羊膜腔显微注射技术，发现注射到羊水中的骨髓间充质干细胞（BMSC）可以自主迁移定植到脊柱裂脊髓的缺损区域，分化为神经元参与神经功能修复，但BMSC定向迁移的数量不能完全满足缺损组织修复的需求。通过对脊柱裂胎鼠脊髓组织进行全转录组测序，发现趋化因子Fractalkine的特异性受体CX3CR1表达显著下调。为进一步增强BMSC靶向修复缺损神经的能力，本课题将包装有CX3CR1的腺病毒注射到脊柱裂胎鼠的羊膜腔，使损伤脊髓CX3CR1表达增多，再移植Fractalkine基因修饰的BMSC，通过Fractalkine/CX3CR1轴调节增强BMSC的靶向迁移能力，激活小胶质细胞的神经保护功能，改善脊髓和羊水的微环境，抑制神经元凋亡，促进突触再生，恢复神经功能，探寻胚胎期微创治疗先天性脊柱裂的新方案。

Congenital spina bifida is one of the common congenital malformations. At present, there is still no effective treatment for the damage of children's neural function. Previously, we established the microinjection technology to the amniotic cavity of rat fetuses. It was found that the injected BMSCs in the amniotic fluid could migrate and engrafted into the defective spinal cord and differentiate into neurons to participate in the repair of neural function, but the number of directional migrated BMSC could not fully meet the repairation of the lesion. Through transcriptome sequencing, CX3CR1, a specific receptor of chemokine fractalkine, was found significantly down regulated in the defective spinal cord. In order to further enhance the ability of BMSC to target and repair the defective neural tissus, the adenovirus-encoding CX3CR1 would be injected into the amniotic cavity of spina bifida fetuses to increase the expression of CX3CR1 in the defective spinal cord, and then the fractalkine-modified BMSCs were transplanted. Through the regulation of fractalkine / CX3CR1 axis, the targeted migration ability of BMSC was enhanced activating the neuroprotective function of microglia, which would help to improve the microenvironment, inhibit neuron apoptosis, promote synaptic regeneration and restore neural function. The purpose of this study is to explore a new method of minimally invasive treatment for congenital spina bifida in embryonic stage.