NanoShuttle改善脂质干细胞治疗神经损伤性勃起功能障碍的分子机制探讨

Recently, erectile dysfunction（ED）post radical prostatectomy is one of the research hotspots and challenges in urological field. Intracavernous injection (ICI) of stem cells has gained great interest as a potential treatment of erectile dysfunction (ED). However, most stem cells were washed out immediately due to the communication between corpus cavernosum (CC) and the blood circulation. In our previous study, novel Nano-ADSCs were created by binding magnetic nanoparticle (NanoShuttle) with adipose derived stem cells (ADSCs), and were successfully kept in CC by magnetic force and improved erectile function in cavernous nerve injury ED model. However, the underlying mechanisms are unclear. Hereby, the aim of this study is to track Nano-ADSCs in vivo and explore the underlying mechanisms of the local kept ADSCs including the mechanisms of the survival way, directional differentiation and paracrine as well as the effect on the NO/cGMP and RhoA/ROCK signal pathways. This study will provide a new idea for treatment of ED post radical prostatectomy.

前列腺癌根治术后勃起功能障碍（ED）的治疗是当今泌尿外科的热点和难点。阴茎海绵体注射（ICI）干细胞治疗ED引起广泛关注，但是绝大多数干细胞在ICI后立即被冲离出阴茎海绵体的问题严重影响治疗效果和机制的研究。前期，我们创新性的使用纳米粒子（NanoShuttle）磁化脂质干细胞（ADSCs）形成（Nano-ADSCs），在磁力的作用下成功的使ICI后的Nano-ADSCs停留在阴茎海绵体局部，并显著增强了干细胞治疗神经损伤性ED的效果。但是局部停留的Nano-ADSCs改善勃起功能的分子机制尚不清楚。因此，本课题将在前期研究的基础上，对ICI后的Nano-ADSCs进行长期活体跟踪观察并进一步探讨局部停留的ADSCs治疗ED的分子机制（定向分化、旁分泌机制的探索、对NO/cGMP信号通路和RhoA/ROCK 信号通路的调节），为临床前列腺癌根治术后ED治疗提供新的思路。

前列腺癌根治术后勃起功能障碍（ED）的治疗是当今泌尿外科的热点和难点。阴茎海绵体注射（ICI）干细胞治疗ED引起广泛关注，但是绝大多数干细胞在ICI后立即被冲离出阴茎海绵体的问题严重影响治疗效果和机制的研究。在前期研究的基础上，我们使用纳米粒子（NanoShuttle）磁化脂质干细胞（ADSCs）形成（Nano-ADSCs），并对Nano-ADSCs进行标记，进行活体追踪，进一步证实纳米技术能有效的增加ADSCs在阴茎海绵体局部的停留的数量和时间。在此基础上，我们还研究了纳米技术优化小剂量ADSCs ICI治疗神经损伤性ED的效果，并对其分子机制进行探索，发现其改善勃起功能的作用机制与α-SMA，CD31，β III Tubulin等的表达信号上调有关。本研究的结果可为临床前列腺癌根治术后ED的干细胞治疗提供新的思路。