神经病理性疼痛的治疗至今尚无突破性进展，基于干细胞作为运载载体的生物治疗模式被视为改善预后的新希望。我们前期工作证实，VEGF189可以明显抑制TRPV1，缓解疼痛。然而上述研究中，病毒载体产生VEGF189的过程不具可控性，由于剂量累积和分布的随机性，其可能对正常脑组织存在不利影响。本项目拟在前期研究基础上改进方法，利用自身脂肪间充质干细胞（ADMSC）作为新载体，并将疼痛相关区域神经元高表达的BDNF作为触发信号，构建可控性靶向释放系统GRB2-VEGF189-ADMSCs，从而使ADMSCs在识别疼痛区域神经元表达异常水平的BDNF后才启动VEGF189的表达，在正常区域不表达或低表达VEGF189，进而实现对靶向药物的可控分泌。同时通过荧光标记和分子生物学技术验证上述载体系统在体内外抑制神经病理性疼痛的效果及相关机制，为ADMSCs治疗疼痛的进一步应用提供理论依据。

Neuropathic pain (NeuP) is still considered as a highly unmet medical need despite current best treatment practices. Therefore, stem cells, whose intrinsic ability are to deliver therapeutic genes or proteins, have been regarded as a new therapeutic prospect for NeuP. Our previous studies have shown that vascular endothelial growth factor (VEGF189) could suppress Transient Receptor Potential cation channel, subfamily V member1 (TRPV1), and alleviate pain. However, the secretion of VEGF189 in the former study is not under control, which means that the VEGF189 can activate all the intracranial TRPV1. It remains unclear whether the VEGF189 or the TRPV1 has negative effects on the normal brain tissue. The goal of this project is to establish engineered Adipose-derived mesenchymal stem cells (ADMSCs) (GRB2-VEGF189-ADMSCs) which can be used as a selective delivery vehicle of VEGF189 under a “switch” of BDNF. Thus, the ADMSCs will express VEGF189 under high level of BDNF in sensory neurons. Meanwhile, they will not secret or rarely secret VEGF189 when they locate normal area. Moreover, luciferase or molecular assay will be performed to determine whether GRB2-VEGF189-ADMSCs under the control of BDNF have an anti-pain response in vitro and in vivo and the involved mechanisms. This study may provide insight into improving the clinical efficacy of ADMSCs for the treatment of NeuP.