Pan Xiaoying, Xing Xiaowen, Ji Zhengguo, Zhang Jianzhong, Chen Qiaomi, Yin Weifan, Zang Yueyue, Yang Yong, Liu Zhiqiang, Xu Yongde
Department of Urology, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130021, China.
Beijing Institute of Basic Medical Sciences, No. 27 Taiping Road, Haidian District, Beijing 100850, PR China.
J Control Release. 2025 Mar 10;379:409-420. doi: 10.1016/j.jconrel.2025.01.002. Epub 2025 Jan 16.
We previously established an effective method to ameliorate erectile dysfunction (ED) using intracavernous injection (ICI) of mesenchymal stem cell (MSC) microspheres. However, the expression of a key neurotrophic factor, brain-derived neurotrophic factor (BDNF), was low in both MSCs and MSC microspheres, restricting the associated neural repair. Based on the hypoxia and oxidative stress microenvironments within cell spheroids and lesion areas, BDNF-expressing nanocomplexes that are dual-responsive to hypoxia and reactive oxygen species were designed to modify MSCs, achieving high BDNF expression in MSC spheroids. Using the pelvic ganglion as an in vitro model, conditioned medium derived from stimuli-responsive MSC microspheres (SRMs) significantly promoted the growth of axons and alleviated the death of neural and smooth muscle cells. In rats with diabetes-induced ED, SRMs that underwent ICI effectively remained in the penis, demonstrating a potent therapeutic outcome. Penile erectile function, smooth muscle content, and neuropathological changes improved after treatment with SRMs compared to unmodified MSCs.
我们之前建立了一种有效的方法，即通过海绵体内注射间充质干细胞（MSC）微球来改善勃起功能障碍（ED）。然而，关键神经营养因子脑源性神经营养因子（BDNF）在MSC和MSC微球中的表达均较低，限制了相关的神经修复。基于细胞球体和损伤区域内的缺氧和氧化应激微环境，设计了对缺氧和活性氧具有双重响应的表达BDNF的纳米复合物来修饰MSC，从而在MSC球体中实现了BDNF的高表达。以盆腔神经节作为体外模型，来自刺激响应性MSC微球（SRM）的条件培养基显著促进了轴突生长，并减轻了神经和平滑肌细胞的死亡。在糖尿病诱导的ED大鼠中，接受海绵体内注射的SRM有效地保留在阴茎中，显示出强大的治疗效果。与未修饰的MSC相比，用SRM治疗后阴茎勃起功能、平滑肌含量和神经病理变化均得到改善。
