Ji-Kan Ryu and Munkhbayar Tumurbaatar contributed equally to this study.
Intracavernous Delivery of Freshly Isolated Stromal Vascular Fraction Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse
Article first published online: 22 OCT 2012
© 2012 International Society for Sexual Medicine
The Journal of Sexual Medicine
Volume 9, Issue 12, pages 3051–3065, December 2012
How to Cite
Ryu, J.-K., Tumurbaatar, M., Jin, H.-R., Kim, W. J., Kwon, M.-H., Piao, S., Choi, M. J., Yin, G. N., Song, K.-M., Kang, Y.-J., Koh, Y. J., Koh, G. Y. and Suh, J.-K. (2012), Intracavernous Delivery of Freshly Isolated Stromal Vascular Fraction Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse. Journal of Sexual Medicine, 9: 3051–3065. doi: 10.1111/j.1743-6109.2012.02962.x
- Issue published online: 3 DEC 2012
- Article first published online: 22 OCT 2012
- Diabetes Mellitus;
- Erectile Dysfunction;
- Endothelial Dysfunction;
- Adipose Tissue;
- Stem Cells;
- Cell Therapy;
- Stromal Vascular Fraction;
Introduction. Men with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors.
Aim. To examine whether and how freshly isolated stromal vascular fraction (SVF) promotes cavernous endothelial regeneration and restores erectile function in diabetic animals.
Methods. Eight-week-old C57BL/6J mice were used. Diabetes was induced by intraperitoneal injection of streptozotocin. SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice. At 8 weeks after the induction of diabetes, the animals were divided into six groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 × 104 cells, 1 × 105 cells, or 2 × 105 cells/20 µL, respectively).
Main Outcome Measures. Two weeks later, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to CD31, CD34, phosphohistone H3, phospho-endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor-A (VEGF-A). We also performed Western blot for phospho-eNOS and eNOS, and determined cyclic guanosine monophosphate (cGMP) concentration in the corpus cavernosum tissue.
Results. Significant improvement in erectile function was noted in diabetic mice treated with SVF at concentrations of 1 × 105 and 2 × 105 cells, which reached up to 82% of the control values. Local delivery of SVF significantly increased cavernous endothelial cell proliferation, eNOS phosphorylation, and cGMP expression compared with that in the untreated group and the PBS-treated diabetic group. Intracavernous injection of SVF increased cavernous VEGF-A expression and induced recruitment of CD34(+)CD31(−) progenitor cells. Some SVF underwent differentiation into cavernous endothelial cells. SVF-induced promotion of cavernous angiogenesis and erectile function was abolished in the presence of VEGF-Trap, a soluble VEGF-A neutralizing antibody.
Conclusion. The results support the concept of cavernous endothelial regeneration by use of SVF as a curative therapy for diabetic ED. Ryu J-K, Tumurbaatar M, Jin H-R, Kim WJ, Kwon M-H, Piao S, Choi MJ, Yin GN, Song K-M, Kang Y-J, Koh YJ, Koh GY, and Suh J-K. Intracavernous delivery of freshly isolated stromal vascular fraction rescues erectile function by enhancing endothelial regeneration in the streptozotocin-induced diabetic mouse. J Sex Med 2012;9:3051–3065.