Korean J Urol.  2015 Apr;56(4):257-265. 10.4111/kju.2015.56.4.257.

Prospects of stem cell treatment in benign urological diseases

• Alwaal A
• Hussein AA
• Lin CS
• Lue TF

• KMID: 2155300
• DOI: http://doi.org/10.4111/kju.2015.56.4.257

Abstract

Stem cells (SCs) are undifferentiated cells that are capable of self-renewal and differentiation and that therefore contribute to the renewal and repair of tissues. Their capacity for division, differentiation, and tissue regeneration is highly dependent on the surrounding environment. Several preclinical and clinical studies have utilized SCs in urological disorders. In this article, we review the current status of SC use in benign urological diseases (erectile dysfunction, Peyronie disease, infertility, and urinary incontinence), and we summarize the results of the preclinical and clinical trials that have been conducted.

Keyword

Erectile dysfunction; Infertility; Stem cells; Urinary incontinence

MeSH Terms

Erectile Dysfunction/physiopathology/*therapy
Female
Humans
Male
Outcome Assessment (Health Care)
Stem Cell Transplantation/*methods
Urinary Incontinence/physiopathology/*therapy

Reference

1. Lin CS, Xin ZC, Deng CH, Ning H, Lin G, Lue TF. Recent advances in andrology-related stem cell research. Asian J Androl. 2008; 10:171–175.

2. Alwaal A, Zaid UB, Lin CS, Lue TF. Stem cell treatment of erectile dysfunction. Adv Drug Deliv Rev. 2014; 11. 14. [Epub]. http://dx.doi.org/10.1016/j.addr.2014.11.012.

3. Kiefer JC. Primer and interviews: The dynamic stem cell niche. Dev Dyn. 2011; 240:737–743.

4. Sanchez-Cruz JJ, Cabrera-Leon A, Martin-Morales A, Fernandez A, Burgos R, Rejas J. Male erectile dysfunction and health-related quality of life. Eur Urol. 2003; 44:245–253.

5. Laumann EO, West S, Glasser D, Carson C, Rosen R, Kang JH. Prevalence and correlates of erectile dysfunction by race and ethnicity among men aged 40 or older in the United States: from the male attitudes regarding sexual health survey. J Sex Med. 2007; 4:57–65.

6. Carvalheira AA, Pereira NM, Maroco J, Forjaz V. Dropout in the treatment of erectile dysfunction with PDE5: a study on predictors and a qualitative analysis of reasons for discontinuation. J Sex Med. 2012; 9:2361–2369.

7. Lin CS, Xin Z, Dai J, Huang YC, Lue TF. Stem-cell therapy for erectile dysfunction. Expert Opin Biol Ther. 2013; 13:1585–1597.

8. Carrier S, Nagaraju P, Morgan DM, Baba K, Nunes L, Lue TF. Age decreases nitric oxide synthase-containing nerve fibers in the rat penis. J Urol. 1997; 157:1088–1092.

9. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol. 2005; 174:386–393.

10. Wespes E. Erectile dysfunction in the ageing man. Curr Opin Urol. 2000; 10:625–628.

11. Dashwood MR, Crump A, Shi-Wen X, Loesch A. Identification of neuronal nitric oxide synthase (nNOS) in human penis: a potential role of reduced neuronally-derived nitric oxide in erectile dysfunction. Curr Pharm Biotechnol. 2011; 12:1316–1321.

12. Huang YC, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, et al. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med. 2010; 7(4 Pt 1):1391–1400.

13. Ficarra V, Novara G, Artibani W, Cestari A, Galfano A, Graefen M, et al. Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies. Eur Urol. 2009; 55:1037–1063.

14. Fode M, Ohl DA, Ralph D, Sonksen J. Penile rehabilitation after radical prostatectomy: what the evidence really says. BJU Int. 2013; 112:998–1008.

15. Carrier S, Hricak H, Lee SS, Baba K, Morgan DM, Nunes L, et al. Radiation-induced decrease in nitric oxide synthase: containing nerves in the rat penis. Radiology. 1995; 195:95–99.

16. Bochinski D, Lin GT, Nunes L, Carrion R, Rahman N, Lin CS, et al. The effect of neural embryonic stem cell therapy in a rat model of cavernosal nerve injury. BJU Int. 2004; 94:904–909.

17. Gou X, He WY, Xiao MZ, Qiu M, Wang M, Deng YZ, et al. Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats. Asian J Androl. 2011; 13:332–338.

18. Qiu X, Lin H, Wang Y, Yu W, Chen Y, Wang R, et al. Intracavernous transplantation of bone marrow-derived mesenchymal stem cells restores erectile function of streptozocin-induced diabetic rats. J Sex Med. 2011; 8:427–436.

19. Fall PA, Izikki M, Tu L, Swieb S, Giuliano F, Bernabe J, et al. Apoptosis and effects of intracavernous bone marrow cell injection in a rat model of postprostatectomy erectile dysfunction. Eur Urol. 2009; 56:716–725.

20. Bivalacqua TJ, Deng W, Kendirci M, Usta MF, Robinson C, Taylor BK, et al. Mesenchymal stem cells alone or ex vivo gene modified with endothelial nitric oxide synthase reverse age-associated erectile dysfunction. Am J Physiol Heart Circ Physiol. 2007; 292:H1278–H1290.

21. Hwang JH, Yuk SH, Lee JH, Lyoo WS, Ghil SH, Lee SS, et al. Isolation of muscle derived stem cells from rat and its smooth muscle differentiation [corrected]. Mol Cells. 2004; 17:57–61.

22. Kim Y, de Miguel F, Usiene I, Kwon D, Yoshimura N, Huard J, et al. Injection of skeletal muscle-derived cells into the penis improves erectile function. Int J Impot Res. 2006; 18:329–334.

23. Song YS, Lee HJ, Park IH, Lim IS, Ku JH, Kim SU. Human neural crest stem cells transplanted in rat penile corpus cavernosum to repair erectile dysfunction. BJU Int. 2008; 102:220–224.

24. Qiu X, Fandel TM, Ferretti L, Albersen M, Orabi H, Zhang H, et al. Both immediate and delayed intracavernous injection of autologous adipose-derived stromal vascular fraction enhances recovery of erectile function in a rat model of cavernous nerve injury. Eur Urol. 2012; 62:720–727.

25. Ryu JK, Tumurbaatar M, Jin HR, Kim WJ, Kwon MH, Piao S, et al. 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.

26. 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; 6:967–979.

27. Ouyang B, Sun X, Han D, Chen S, Yao B, Gao Y, et al. Human urine-derived stem cells alone or genetically-modified with FGF2 Improve type 2 diabetic erectile dysfunction in a rat model. PLoS One. 2014; 9:e92825.

28. Qiu X, Villalta J, Ferretti L, Fandel TM, Albersen M, Lin G, et al. Effects of intravenous injection of adipose-derived stem cells in a rat model of radiation therapy-induced erectile dysfunction. J Sex Med. 2012; 9:1834–1841.

29. Kim SJ, Choi SW, Hur KJ, Park SH, Sung YC, Ha YS, et al. Synergistic effect of mesenchymal stem cells infected with recombinant adenovirus expressing human BDNF on erectile function in a rat model of cavernous nerve injury. Korean J Urol. 2012; 53:726–732.

30. Choi WY, Jeon HG, Chung Y, Lim JJ, Shin DH, Kim JM, et al. Isolation and characterization of novel, highly proliferative human CD34/CD73-double-positive testis-derived stem cells for cell therapy. Stem Cells Dev. 2013; 22:2158–2173.

31. You D, Jang MJ, Lee J, Jeong IG, Kim HS, Moon KH, et al. Periprostatic implantation of human bone marrow-derived mesenchymal stem cells potentiates recovery of erectile function by intracavernosal injection in a rat model of cavernous nerve injury. Urology. 2013; 81:104–110.

32. You D, Jang MJ, Lee J, Suh N, Jeong IG, Sohn DW, et al. Comparative analysis of periprostatic implantation and intracavernosal injection of human adipose tissue-derived stem cells for erectile function recovery in a rat model of cavernous nerve injury. Prostate. 2013; 73:278–286.

33. Ryu JK, Kim DH, Song KM, Yi T, Suh JK, Song SU. Intracavernous delivery of clonal mesenchymal stem cells restores erectile function in a mouse model of cavernous nerve injury. J Sex Med. 2014; 11:411–423.

34. Smith JF, Walsh TJ, Conti SL, Turek P, Lue T. Risk factors for emotional and relationship problems in Peyronie's disease. J Sex Med. 2008; 5:2179–2184.

35. Gonzalez-Cadavid NF, Rajfer J. Mechanisms of disease: new insights into the cellular and molecular pathology of Peyronie's disease. Nat Clin Pract Urol. 2005; 2:291–297.

36. Devine CJ Jr. International Conference on Peyronie's disease advances in basic and clinical research. March 17-19, 1993. Introduction. J Urol. 1997; 157:272–275.

37. Gonzalez-Cadavid NF, Magee TR, Ferrini M, Qian A, Vernet D, Rajfer J. Gene expression in Peyronie's disease. Int J Impot Res. 2002; 14:361–374.

38. Tal R, Heck M, Teloken P, Siegrist T, Nelson CJ, Mulhall JP. Peyronie's disease following radical prostatectomy: incidence and predictors. J Sex Med. 2010; 7:1254–1261.

39. Vernet D, Nolazco G, Cantini L, Magee TR, Qian A, Rajfer J, et al. Evidence that osteogenic progenitor cells in the human tunica albuginea may originate from stem cells: implications for peyronie disease. Biol Reprod. 2005; 73:1199–1210.

40. Shindel AW. Sexual dysfunction: The potential of stem cell therapy for Peyronie disease. Nat Rev Urol. 2013; 10:8–9.

41. Lin CS, Lin G, Lue TF. Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev. 2012; 21:2770–2778.

42. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells. 2007; 25:2739–2749.

43. Zhang H, Ning H, Banie L, Wang G, Lin G, Lue TF, et al. Adipose tissue-derived stem cells secrete CXCL5 cytokine with chemoattractant and angiogenic properties. Biochem Biophys Res Commun. 2010; 402:560–564.

44. Castiglione F, Hedlund P, Van der Aa F, Bivalacqua TJ, Rigatti P, Van Poppel H, et al. Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie's disease. Eur Urol. 2013; 63:551–560.

45. Schover LR, Brey K, Lichtin A, Lipshultz LI, Jeha S. Oncologists' attitudes and practices regarding banking sperm before cancer treatment. J Clin Oncol. 2002; 20:1890–1897.

46. Meistrich ML, Finch M, da Cunha MF, Hacker U, Au WW. Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells. Cancer Res. 1982; 42:122–131.

47. Yokonishi T, Sato T, Komeya M, Katagiri K, Kubota Y, Nakabayashi K, et al. Offspring production with sperm grown in vitro from cryopreserved testis tissues. Nat Commun. 2014; 5:4320.

48. Lin CS, Lue TF. Stem cell therapy for stress urinary incontinence: a critical review. Stem Cells Dev. 2012; 21:834–843.

49. Delancey JO. Why do women have stress urinary incontinence? Neurourol Urodyn. 2010; 29:Suppl 1. S13–S17.

50. Lin CS. Stem cell therapy for the bladder: where do we stand? J Urol. 2011; 185:779–780.

51. Lin G, Wang G, Banie L, Ning H, Shindel AW, Fandel TM, et al. Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy. 2010; 12:88–95.

52. Chancellor MB, Yokoyama T, Tirney S, Mattes CE, Ozawa H, Yoshimura N, et al. Preliminary results of myoblast injection into the urethra and bladder wall: a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility. Neurourol Urodyn. 2000; 19:279–287.

53. Yiou R, Dreyfus P, Chopin DK, Abbou CC, Lefaucheur JP. Muscle precursor cell autografting in a murine model of urethral sphincter injury. BJU Int. 2002; 89:298–302.

54. Corcos J, Loutochin O, Campeau L, Eliopoulos N, Bouchentouf M, Blok B, et al. Bone marrow mesenchymal stromal cell therapy for external urethral sphincter restoration in a rat model of stress urinary incontinence. Neurourol Urodyn. 2011; 30:447–455.

55. Kinebuchi Y, Aizawa N, Imamura T, Ishizuka O, Igawa Y, Nishizawa O. Autologous bone-marrow-derived mesenchymal stem cell transplantation into injured rat urethral sphincter. Int J Urol. 2010; 17:359–368.

56. Kim SO, Na HS, Kwon D, Joo SY, Kim HS, Ahn Y. Bone-marrow-derived mesenchymal stem cell transplantation enhances closing pressure and leak point pressure in a female urinary incontinence rat model. Urol Int. 2011; 86:110–116.

57. Zou XH, Zhi YL, Chen X, Jin HM, Wang LL, Jiang YZ, et al. Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence. Biomaterials. 2010; 31:4872–4879.

58. Dissaranan C, Cruz MA, Kiedrowski MJ, Balog BM, Gill BC, Penn MS, et al. Rat mesenchymal stem cell secretome promotes elastogenesis and facilitates recovery from simulated childbirth injury. Cell Transplant. 2014; 23:1395–1406.

59. Lee CN, Jang JB, Kim JY, Koh C, Baek JY, Lee KJ. Human cord blood stem cell therapy for treatment of stress urinary incontinence. J Korean Med Sci. 2010; 25:813–816.

60. Fu Q, Song XF, Liao GL, Deng CL, Cui L. Myoblasts differentiated from adipose-derived stem cells to treat stress urinary incontinence. Urology. 2010; 75:718–723.

61. Watanabe T, Maruyama S, Yamamoto T, Kamo I, Yasuda K, Saka Y, et al. Increased urethral resistance by periurethral injection of low serum cultured adipose-derived mesenchymal stromal cells in rats. Int J Urol. 2011; 18:659–666.

62. Wu G, Song Y, Zheng X, Jiang Z. Adipose-derived stromal cell transplantation for treatment of stress urinary incontinence. Tissue Cell. 2011; 43:246–253.

63. Zhao W, Zhang C, Jin C, Zhang Z, Kong D, Xu W, et al. 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. Eur Urol. 2011; 59:155–163.

64. Li GY, Zhou F, Gong YQ, Cui WS, Yuan YM, Song WD, et al. Activation of VEGF and ERK1/2 and improvement of urethral function by adipose-derived stem cells in a rat stress urinary incontinence model. Urology. 2012; 80:953.e1–953.e8.

65. Shi LB, Cai HX, Chen LK, Wu Y, Zhu SA, Gong XN, et al. Tissue engineered bulking agent with adipose-derived stem cells and silk fibroin microspheres for the treatment of intrinsic urethral sphincter deficiency. Biomaterials. 2014; 35:1519–1530.

66. Kim BS, Chun SY, Lee JK, Lim HJ, Bae JS, Chung HY, et al. Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model. BMC Med. 2012; 10:94.

67. Chun SY, Cho DH, Chae SY, Choi KH, Lim HJ, Yoon GS, et al. Human amniotic fluid stem cell-derived muscle progenitor cell therapy for stress urinary incontinence. J Korean Med Sci. 2012; 27:1300–1307.

68. Chun SY, Kwon JB, Chae SY, Lee JK, Bae JS, Kim BS, et al. Combined injection of three different lineages of early-differentiating human amniotic fluid-derived cells restores urethral sphincter function in urinary incontinence. BJU Int. 2014; 114:770–783.

69. Badra S, Andersson KE, Dean A, Mourad S, Williams JK. Long-term structural and functional effects of autologous muscle precursor cell therapy in a nonhuman primate model of urinary sphincter deficiency. J Urol. 2013; 190:1938–1945.

70. Jiang HH, Damaser M. Animal models of stress urinary incontinence. In : Andersson KE, Michel MC, editors. Urinary tract. Berlin: Springer;2011. p. 45–67.

71. Lin AS, Carrier S, Morgan DM, Lue TF. Effect of simulated birth trauma on the urinary continence mechanism in the rat. Urology. 1998; 52:143–151.

72. Sievert KD, Emre Bakircioglu M, Tsai T, Dahms SE, Nunes L, Lue TF. The effect of simulated birth trauma and/or ovariectomy on rodent continence mechanism. Part I: functional and structural change. J Urol. 2001; 166:311–317.

73. Pauwels E, De Wachter S, Wyndaele JJ. Evaluation of different techniques to create chronic urinary incontinence in the rat. BJU Int. 2009; 103:782–785.

74. Rodriguez LV, Chen S, Jack GS, de Almeida F, Lee KW, Zhang R. New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency. Am J Physiol Regul Integr Comp Physiol. 2005; 288:R1332–R1338.

75. Lin YH, Liu G, Li M, Xiao N, Daneshgari F. Recovery of continence function following simulated birth trauma involves repair of muscle and nerves in the urethra in the female mouse. Eur Urol. 2010; 57:506–512.

76. Mitterberger M, Marksteiner R, Margreiter E, Pinggera GM, Colleselli D, Frauscher F, et al. Autologous myoblasts and fibroblasts for female stress incontinence: a 1-year follow-up in 123 patients. BJU Int. 2007; 100:1081–1085.

77. Mitterberger M, Marksteiner R, Margreiter E, Pinggera GM, Frauscher F, Ulmer H, et al. Myoblast and fibroblast therapy for post-prostatectomy urinary incontinence: 1-year followup of 63 patients. J Urol. 2008; 179:226–231.

78. Mitterberger M, Pinggera GM, Marksteiner R, Margreiter E, Fussenegger M, Frauscher F, et al. Adult stem cell therapy of female stress urinary incontinence. Eur Urol. 2008; 53:169–175.

79. Strasser H, Marksteiner R, Margreiter E, Mitterberger M, Pinggera GM, Frauscher F, et al. Transurethral ultrasonography-guided injection of adult autologous stem cells versus transurethral endoscopic injection of collagen in treatment of urinary incontinence. World J Urol. 2007; 25:385–392.

80. Strasser H, Marksteiner R, Margreiter E, Pinggera GM, Mitterberger M, Frauscher F, et al. Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial. Lancet. 2007; 369:2179–2186.

81. Carr LK, Steele D, Steele S, Wagner D, Pruchnic R, Jankowski R, et al. 1-year follow-up of autologous muscle-derived stem cell injection pilot study to treat stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2008; 19:881–883.

82. 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 Urol. 2010; 17:75–82.

83. Sebe P, Doucet C, Cornu JN, Ciofu C, Costa P, de Medina SG, et al. Intrasphincteric injections of autologous muscular cells in women with refractory stress urinary incontinence: a prospective study. Int Urogynecol J. 2011; 22:183–189.

84. Yamamoto T, Gotoh M, Kato M, Majima T, Toriyama K, Kamei Y, et al. Periurethral injection of autologous adipose-derived regenerative cells for the treatment of male stress urinary incontinence: Report of three initial cases. Int J Urol. 2012; 19:652–659.

85. Gotoh M, Yamamoto T, Kato M, Majima T, Toriyama K, Kamei Y, et al. Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients. Int J Urol. 2014; 21:294–300.

86. Stangel-Wojcikiewicz K, Jarocha D, Piwowar M, Jach R, Uhl T, Basta A, et al. Autologous muscle-derived cells for the treatment of female stress urinary incontinence: a 2-year follow-up of a Polish investigation. Neurourol Urodyn. 2014; 33:324–330.

87. Kuismanen K, Sartoneva R, Haimi S, Mannerstrom B, Tomas E, Miettinen S, et al. Autologous adipose stem cells in treatment of female stress urinary incontinence: results of a pilot study. Stem Cells Transl Med. 2014; 3:936–941.

88. Lee JY, Cannon TW, Pruchnic R, Fraser MO, Huard J, Chancellor MB. The effects of periurethral muscle-derived stem cell injection on leak point pressure in a rat model of stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct. 2003; 14:31–37.

89. Yiou R, Yoo JJ, Atala A. Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts. Transplantation. 2003; 76:1053–1060.

90. Cannon TW, Lee JY, Somogyi G, Pruchnic R, Smith CP, Huard J, et al. Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra. Urology. 2003; 62:958–963.

91. Chermansky CJ, Tarin T, Kwon DD, Jankowski RJ, Cannon TW, de Groat WC, et al. Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency. Urology. 2004; 63:780–785.

92. Lee JY, Paik SY, Yuk SH, Lee JH, Ghil SH, Lee SS. Long term effects of muscle-derived stem cells on leak point pressure and closing pressure in rats with transected pudendal nerves. Mol Cells. 2004; 18:309–313.

93. Yiou R, Yoo JJ, Atala A. Failure of differentiation into mature myotubes by muscle precursor cells with the side-population phenotype after injection into irreversibly damaged striated urethral sphincter. Transplantation. 2005; 80:131–133.

94. Kwon D, Kim Y, Pruchnic R, Jankowski R, Usiene I, de Miguel F, et al. Periurethral cellular injection: comparison of muscle-derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence. Urology. 2006; 68:449–454.

95. Kim YT, Kim DK, Jankowski RJ, Pruchnic R, Usiene I, de Miguel F, et al. Human muscle-derived cell injection in a rat model of stress urinary incontinence. Muscle Nerve. 2007; 36:391–393.

96. Hoshi A, Tamaki T, Tono K, Okada Y, Akatsuka A, Usui Y, et al. Reconstruction of radical prostatectomy-induced urethral damage using skeletal muscle-derived multipotent stem cells. Transplantation. 2008; 85:1617–1624.

97. Furuta A, Jankowski RJ, Pruchnic R, Egawa S, Yoshimura N, Chancellor MB. Physiological effects of human muscle-derived stem cell implantation on urethral smooth muscle function. Int Urogynecol J Pelvic Floor Dysfunct. 2008; 19:1229–1234.

98. Lim JJ, Jang JB, Kim JY, Moon SH, Lee CN, Lee KJ. Human umbilical cord blood mononuclear cell transplantation in rats with intrinsic sphincter deficiency. J Korean Med Sci. 2010; 25:663–670.

99. 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; 43:1076–1083.