Therapeutic potential of adipose-derived stem cells-based micro-tissues in a rat model of postprostatectomy erectile dysfunction

Abstract

Introduction: Stem cells (SCs) show significant benefits in the treatment of postprostatectomy erectile dysfunction (ED). However, the low retention rate of the traditional single-cell strategy at the injection sites limits its therapeutic potential.

Aim: This study aims to investigate the feasibility and mechanism of adipose-derived stem cells (ADSCs)-based micro-tissues (MTs) in the treatment of ED in a rat model of bilateral cavernous nerves (CNs) 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 phosphate buffer solution (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 MT, immunohistologic examination of the MTs, the retention and distribution of EdU + ADSCs in the corpus cavernosum (CC), and the penis histological analyses of collagen content, Western blot of functional proteins in MTs, intracavernous pressure recording on CN electrostimulation.

Results: Three-day-old MTs became stable and expressed nerve growth factor, vascular endothelial growth factor, C-X-C chemokine receptor type 4, Wnt5a, and collagen IV. 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 with the ADSCs group.

Conclusion: IC-injected MTs resulted in a better restoration of erectile function than traditional single-cell strategy. The underlying mechanisms of recovery appear to involve enhanced cellular retention in the penis and upregulation of some paracrine factors.

Keywords: Adipose-Derived Stem Cells; Cavernous Nerve Injury; Cellular Retention; Erectile Dysfunction; Hanging Drop; Micro-Tissues; Paracrine Factors; Radical Prostatectomy.