Co-overexpression of VEGF and Smad7 improved the therapeutic effects of adipose-derived stem cells on neurogenic erectile dysfunction in the rat model

Andrologia. 2022 Nov;54(10):e14538. doi: 10.1111/and.14538. Epub 2022 Aug 1.

Abstract

Cavernous nerve injury is the main cause of erectile dysfunction (ED) after radical prostatectomy (RP). In our previous study, injection of adipose-derived stem cells (ADSCs) into the cavernosum can repair damaged cavernosum nerves and ED can be restored to a certain extent. In order to improve these therapeutic effects, we evaluated the efficacy of ADSCs co-modified with VEGF and Smad7 in a rat model. SD rats were randomly divided into six groups: a sham surgery group, and the five bilateral cavernous nerve injury (BCNI) groups were injected with ADSC or ADSCs genetically modified by VEGF (ADSC-V), Smad7 (ADSC-S), or VEGF&Smad7 (ADSC-V&S) or phosphate-buffered saline (PBS). The results indicated that the erectile function of the ADSC-V, ADSC-S, and ADSC-V&S groups was significantly recovered, and the erectile function of the ADSC-V&S group was more distinctly recovered as compared to the other groups. The same results are shown in the expression of neuronal nitric oxide synthase and the smooth muscle/collagen ratio of penile tissue comparing the ADSC-V&S group to the ADSC-V and ADSC-S group. These experimental data suggest that ADSCs co-overexpressed with VEGF and Smad7 can significantly improve erectile function after BCNI. This study provides new therapeutic thoughts for ED following RP.

Keywords: Smad7; VEGF; adipose-derived stem cells; neurogenic erectile dysfunction; stem cell therapy.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Collagen
  • Disease Models, Animal
  • Erectile Dysfunction* / etiology
  • Erectile Dysfunction* / therapy
  • Humans
  • Male
  • Nitric Oxide Synthase Type I / metabolism
  • Penile Erection
  • Penis
  • Phosphates / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Smad7 Protein / metabolism
  • Stem Cell Transplantation / methods
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Phosphates
  • SMAD7 protein, human
  • Smad7 Protein
  • Smad7 protein, rat
  • Vascular Endothelial Growth Factor A
  • Collagen
  • Nitric Oxide Synthase Type I