Xenogenic transplantation of human breast adipose-derived stromal vascular fraction enhances recovery of erectile function in diabetic mice

Biol Reprod. 2014 Mar 27;90(3):66. doi: 10.1095/biolreprod.113.115113. Print 2014 Mar.

Abstract

The adipose tissue-derived stromal vascular fraction (SVF) is an ideal source of stem and stromal cells. The aim of this study was to examine whether and how xenogenic transplantation of human breast SVF restores erectile function in diabetic mice. Human SVF was isolated from five patients (age, 20-45 yr) undergoing reduction mammoplasty. Eight-week-old C57BL/6J mice were used, and diabetes was induced by intraperitoneal injection of streptozotocin. At 8 wk after induction of diabetes, the animals were randomly distributed into controls and diabetic mice treated with a single intracavernous injection of PBS, human SVF at different concentrations, or human SVF lysate. Two weeks later, erectile function was measured by cavernous nerve stimulation, and the penis was then harvested for biochemical examinations. Erectile function was significantly improved in diabetic mice treated with human SVF (2 × 10(5), 5 × 10(5), and 1 × 10(6) cells/20 μl) and SVF lysate. Human SVF treatment in diabetic mice significantly increased cavernous endothelial and smooth muscle cell contents, induced eNOS phosphorylation, and restored penile nNOS-positive nerve fibers. Human SVF lysate induced secretion of angiogenic factors and expression of their receptors. Human SVF did not increase serum levels of proinflammatory cytokines. A limitation of this study was that the exact composition of the human SVF was not examined. In summary, xenogenic transplantation of human SVF did not induce systemic inflammation and successfully improved erectile function in diabetic mice through enhanced penile angiogenesis and neural regeneration.

Keywords: angiogenesis; breast tissue; cell therapy; diabetes mellitus; erectile dysfunction; male sexual function; stromal vascular fraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry*
  • Adipose Tissue / transplantation*
  • Adult
  • Angiogenic Proteins / biosynthesis
  • Animals
  • Blotting, Western
  • Breast / physiology
  • Breast / transplantation*
  • Cell Transplantation / methods*
  • Diabetes Mellitus, Experimental / complications*
  • Erectile Dysfunction / etiology*
  • Erectile Dysfunction / therapy*
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-6 / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Nitric Oxide Synthase Type III / metabolism
  • Penile Erection / physiology
  • Penis / metabolism
  • Phosphorylation
  • Stromal Cells / physiology*
  • Transplantation, Heterologous / methods*
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult

Substances

  • Angiogenic Proteins
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type III