Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats

Asian J Androl. 2017 Jan-Feb;19(1):91-97. doi: 10.4103/1008-682X.182817.

Abstract

This study aimed to explore the therapeutic effects of adipose-derived stem cells (ADSCs)-based microtissues (MTs) on erectile dysfunction (ED) in streptozotocin (STZ)-induced diabetic rats. Fifty-six 8-week-old Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg kg-1 ), and 8 weeks later, the determined diabetic rats randomly received intracavernous (IC) injection of phosphate buffer solution (PBS), ADSCs, or MTs. Another eight normal rats equally got IC injection of PBS. MTs were generated with a hanging drop method, and the injected cells were tracked in ADSC- and MT-injected rats. Four weeks after the treatments, intracavernous pressure (ICP), histopathological changes in corpus cavernosum (CC), and functional proteins were measured. Rat cytokine antibody array was used to detect ADSCs or MTs lysate. The results showed that MTs expressed vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and tumor necrosis factor-stimulated gene-6 (TSG-6). MTs injection had a higher retention than ADSCs injection and MTs treatment improved ICP, neuronal nitric oxide synthase (nNOS) expression, smooth muscle, and endothelial contents in diabetic rats, ameliorated local inflammation in CC better. Thus, our findings demonstrate that IC injection of MTs improves erectile function and histopathological changes in STZ-induced diabetic rats and appears to be more promising than traditional ADSCs. The underlying mechanisms involve increased cell retention accompanied with neuroprotection and anti-inflammatory behaviors of the paracrine factors.

MeSH terms

  • Actins / metabolism
  • Adipose Tissue / cytology*
  • Animals
  • Blotting, Western
  • Cell Adhesion Molecules / metabolism
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / metabolism
  • Disease Models, Animal
  • Erectile Dysfunction / etiology
  • Erectile Dysfunction / metabolism
  • Erectile Dysfunction / therapy*
  • Fluorescent Antibody Technique
  • Male
  • NF-kappa B / metabolism
  • Nerve Growth Factor / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • Penile Erection*
  • Penis / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Actins
  • Cell Adhesion Molecules
  • NF-kappa B
  • Tnfaip6 protein, rat
  • Vascular Endothelial Growth Factor A
  • smooth muscle actin, rat
  • vascular endothelial growth factor A, rat
  • Nerve Growth Factor
  • Nitric Oxide Synthase Type I