Published 2015-04-01
Endi Prilansa Mahadi Sunaryo Hardjowijoto Sabilal Alif Purwati Purwati Willy Sandhika Budiono Budiono


Objective: To examine the effects of adipose-derived stem cell (ADSC) transplantation on urethral tissue microvessel and voiding function on artificial stress urinary incontinence (SUI) in rats. Material & methods: 25 of 32 female wistar rats underwent vaginal distension as animal-SUI model. ADSCs were isolated from the peri-ovary fat, examined for stem cell properties, and labeled with PKH-2. Seven rats without vaginal distension and periurethral ADSCs injection as control. Twelve rats received periurethral injection of phosphate buffer saline as plasebo and 13 rats received periurethral injection of ADSCs. 14 and 28 days later, voided volume was meassured with voided stained on paper and microvessel density was meassured with immunohistochemical analysis (factor VIII R-Ag). Results: Voided volume analysis showed that rats in the plasebo group had abnormal voided volume compare to normal rats in day 14 (168.5 ± 119.05l vs 621.21 ± 283.85l; p < 0.05), and insignificant improvement of voided volume compare to normal rats in day 28 (852.09 ± 626.7l vs 868.49 ± 578.0l; p > 0.05). While in the ADSCs group only showed significant improvement of voided volume compare to abnormal rats in days 14 (379.35 ± 191.74l vs 228.18 ± 56.26l; p < 0.05). Immunohistochemical analysis showed that microvessel density higher in the ADSCs group compare to plasebo group in days 28 (12.86 ± 2.5 vs 9.50 ± 1.64; p < 0.05). Conclusion: ADSCs transplantation promotes improvements voided volume and urethral microvessel in the rat-SUI model. Keywords: Adipose-derived stem cell, vaginal distension, voided stained on paper, microvessel density.



Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology of lower urinary tract function: Report from the standardisation sub-committee of the international continence society. Neurourology and Urodynamics. 2002; 21: 167-78.

Chapple CR. Milsom I. Urinary incontinence and pelvic prolapse: Epidemiology and pathophsiology. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (ed). Campbell-Walsh Urology, 10th ed. Philadelphia: Elsevier-Saunders; 2012. p. 1871-95.

Hunskaar S, Burgio K, Diokno A, Herzog AR, Hjalmås K, Lapitan MC. Epidemiology and natural history of urinary incontinence in women. Urology. 2003; 62 (Suppl 4A): 16-23.

Dooley Y, Kenton K, Cao G, Luke A, Durazo-Arvizu R, Kramer H, et al. Urinary incontinence. Prevalence: Results From the National Health and Nutrition Examination Survey. J Urol. 2007; 179: 656-61.

Chapple CR, Bhargava S, Andersson KE. Medical, behavioral and minimally invasive therapy - a urologist’s view. In: Becker HD, Stenzl A, Wallwiener D, Zittel TT (ed). Urinary and Fecal Incontinence, An Interdisciplinary Approach. Berlin Heidelberg: Springer-Verlag; 2005. p. 182-96.

Payne CK. Conservative management of urinary Iincontinence: Behavioral and pelvic floor therapy, urethral and pelvic devices. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (Ed). Campbell-Walsh Urology, 10th ed. Philadelphia: Elsevier-Sounders; 2012. p. 2004-25.

Fu Q, Song XF, Liao GL, Deng CL, Cui L. Myoblasts differentiated from adipose-derived stem cells to treat stress urinary incontinence. J Urol. 2009; 75: 718-23.

Lin G, Wang G, Banie L. Treatment of stress urinary incontinence with adipose tissue derived stem cells. Cytotherapy. 2010; 1: 88-95.

Zhao W, Zhang C, Jin C, Zhang C, Kong D, Xu W. Periurethral injection of autologous adipose-derived stem cells with controlled-release nerve growth factor for the treatment of stress urinary incontinence in a rat model. Euro Urol. 2011; 59: 155-63.

Mitterberger M, Pinggera GM, Marksteiner R, Margreiter E, Fussenegger M, Frauscher F, et al. Adult stem cell therapy of female stress urinary incontinence. Euro Urol. 2008; 53: 169-75.

Yamamoto T, Gotoh M, Hattori R, Toriyama K, Kamei Y, Iwaguro H, et al. Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: Report of two initial cases. Int. J Uro. 2010; 17: 75-82.

Lin AS, Carrier S, Morgan DM, Lue TF. Effect of simulated birth trauma on the urinary continence mechanism in the rat. Urology. 1998; 52: 143-51.

Cannon TW, Wojcik E, Ferguson, C, Saraga S, Thomas C, Damaser M. Effect of vaginal distention on urethral anatomy and function. BJU Int. 2002; 90: 403-7.

Sugino Y, Kanematsu A, Hayashi, Haga H, Yoshimura N, Yoshimura K. Voided stain on paper method for analysis of mouse urination. Neurourol. Urodynam. 2008; 7: 548–52.

Heidkamp MC, Leong FC, Brubaker L, Russell B. Pudendal denervation affects the structure and function of the striated urethral sphincter in female rats. Int Urogynecol J. 1998; 9: 88-93.

Xu Y, Song YF, Lin ZX. Transplantation of muscle-derived stem cells plus biodegradable fibrin glue restores the urethral sphincter in a pudendal nerve-transected rat model. Braz. J. Med. Biol. Res. 2010; 43: 1076-83.

Yamamoto N, Akamatsu H, Hasegawa S, Yamada T, Nakata S, Ohkuma M, et al. Isolation of multipotent stem cells from mouse adipose tissue. Journal of Dermatological Science. 2007; 48: 43-52.

Phillips C, Monga A. Childbirth and the pelvic floor: ‘‘the gynaecological consequences’’. Reviews in Gynaecological Practice. 2005; 5: 15–22.

Obinata D, Matsumoto T, Ikado Y. Transplantation of mature adipocyte-derived dedifferentiated fat (DFAT) cells improve urethral sphincter contractility in a rat model. Int. J. Urol. 2011; 18: 827-34.

Damaser MS, Whitbeck C, Chichester P, Levin RM. Effect of vaginal distension on blood flow and hypoxia of urogenital organs of the female rat. J Appl Physiol. 2005; 98: 1884-90.

Prantil RL, Jankowski RJ, Kalho Y, De Groat WC, Chancellor MB, Yoshimura N, et al. Ex vivo biomechanical properties of the female urethra in a rat model of birth trauma. Am J Physiol Renal Physiol. 2006; 292: 1229-37.

Kilroy GE, Foster SJ, Wu X, Ruiz J, Sherwood S, Heifetz A, et al. Cytokine profile of human adipose-derived stem cells: Expression of angiogenic, hematopoietic, and pro-inflammatory factors. J. Cell. Physiol. 2007; 212: 702-9.

Planat-Benard V, Silvestre J-S, Cousin B, André M, Nibbelink M, Tamarat R. Plasticity of human adipose lineage cells toward endothelial cells: Physiological and therapeutic perspectives. Circulation. 2004; 109: 656-63.

Goldman HB, Sievert KD, Damaser MS. Will we ever use stem cell for the treatment of SUI?: ICI-RS 2011. Neurourology and Urodynamics. 2012; 31: 386-9.

Ning H, Liu G, Lin G, Yang R, Lue TF, Lin CS. Fibroblast growth factor 2 promotes endothelial differentiation of adipose tissue-derived stem cells. J Sex Med. 2009; 6: 967-79.

Copyright Information
Department of Urology, Faculty of Medicine/Airlangga University