Yongde Xu, Ruili Guan, Hongen Lei, Huixi Li, Lin Wang, Zhezhu Gao, Weidong Song, Zhongcheng Xin
Introduction: Stem cells (SCs) show significant benefits in the treatment of post-prostatectomy erectile dysfunction (ED). However, the low retention rate of the traditional single cell strategy at the injection sites limits its therapeutic potential.
Aim: To investigate the feasibility and mechanism of ADSCs based micro-tissues (MTs) in the treatment of ED in a rat model of bilateral cavernous nerves (CN) injury.
Methods: ADSCs labeled with 5-ethynyl-2-deoxyuridine (EdU) were used to generate MTs with hanging drop method. 10 Sprague-Dawley (SD) rats underwent sham surgery and intracavernous (IC) injection of PBS (the sham group). Another 70 rats underwent bilateral CN crush and were then treated with PBS (n=10, the crush group), dissociated ADSCs (n=30, the ADSCs group), and MTs (n=30, the MTs group) respectively. At day 1, 3, 7, 14 (n=5) and 28 (n=10) postsurgery, specimens were harvested for histology. At day 28, 10 rats in each group were examined for erectile function before tissue harvest.
Main outcome measures: Light microscopy of the dynamic aggregation of the micro-tissue, immunohistologic examination of the MTs, the retention and distribution of EdU+ ADSCs in the corpus cavernosum (CC), and the penishistological analyses of collagen content, western blot of functional proteins in MTs, intracavernous pressure (ICP) recording on CN electrostimulation.
Results: Three-day old MTs became stable and expressed NGF, VEGF, CXCR4, Wnt5a, and ColIV. More EdU+ ADSCs retained in the CC in the MTs group than that in the ADSCs group. IC injection of MTs resulted in significant restoration of the erectile function and histopathological changes compared to the ADSCs group.
Conclusion: IC injected MTs resulted in a better restoration of erectile function than tranditional single cell strategy. The underlying mechanisms of recovery appear to involve enhanced cellular retention in the penis and up-regulation of some paracrine factors.
