Objective: To investigate whether ADSCs are capable of nerve repair in stress urinary incontinence. Material & Methods: Thirty rats were allocated to five groups for receiving a periurethral injection with Phosphate Buffer Saline (PBS) (B1,B2) and Adipose-derived Stem Cells (C1, C2). Functional assessments with Voided Stain on Paper (VSOP) Method were reassessed at 2 and 4 weeks after injection. The rat SUI model was generated by Vaginal Distention (VD). The regeneration of peripheral nerve was evaluated by PGP 9.5 immunohistochemical staining. Results: Results revealed significant peripheral nerve differences between ADSC group and other groups in 28 days using PGP 9.5 staining. Our functional assessment, Voided Stain on Paper (VSOP), showed that ADSC group had significant improvement in 14 days; unfortunately, our 28 days improvement was not substantial. Conclusion: Periurethral injection of ADSCs improves urine pattern in SUI-induced rats and increase the amount of peripheral nerve. This method may be a potential strategy for SUI treatment.
Vaginal Distention, Adipose-derived stem cells, PGP 9.5, Nerve healing periurethral, voided stain on paper
Kobashi KC, Albo ME, Dmochowski RR, Ginsberg DA, Goldman HB, Gomelsky A, et al. Surgical Treatment of Female Stress Urinary Incontinence: AUA/SUFU Guideline. J Urol. 2017 Oct; 198(4): 875–83.
Hampel C, Wienhold D, Benken N, Eggersmann C, Thüroff JW. Definition of overactive bladder and epidemiology of urinary incontinence. Urology. 1997 Dec; 50(6): 4–14.
Anger JT, Saigal CS, Litwin MS, The Urologic Diseases of America Project. The Prevalence of Urinary Incontinence Among Community Dwelling Adult Women: Results From the National Health and Nutrition Examination Survey. J Urol. 2006 Feb; 175(2): 601–4.
Vinker S, Kaplan B, Nakar S, Samuels G, Shapira G, Kitai E. Urinary incontinence in women: prevalence, characteristics and effect on quality of life. A primary care clinic study. Isr Med Assoc J IMAJ. 2001 Sep; 3(9): 663–6.
Berglund A-L, Eisemann M, Lalos O. Personality characteristics of-A stress incontinent women: a pilot study. J Psychosom Obstet Gynecol. 1994 Jan; 15(3): 165–70.
Grimby A, Milsom I, Molander U, Wiklund I, Ekelund P. The Influence of Urinary Incontinence on the Quality of Life of Elderly Women. Age Ageing. 1993; 22(2): 82–9.
Prantil RL, Jankowski RJ, Kaiho 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-Ren Physiol. 2007 Apr; 292(4): F1229–37.
Deng DY, Rutman M, Raz S, Rodriguez LV. Presentation and management of major complications of midurethral slings: Are complications under-reported? Neurourol Urodyn. 2007 Jan; 26(1): 46–52.
Snooks SJ, Swash M, Mathers SE, Henry MM. Effect of vaginal delivery on the pelvic floor: A 5-year follow-up. Br J Surg. 1990 Dec; 77(12): 1358–60.
Lin AS, Carrier S, Morgan DM, Lue TF. Effect of simulated birth trauma on the urinary continence mechanism in the rat. Urology. 1998 Jul; 52(1): 143–51.
Damaser MS, Broxton-King C, Ferguson C, Kim FJ, Kerns JM. Functional and Neuroanatomical Effects of Vaginal Distention and Pudendal Nerve Crush in the Female Rat. J Urol. 2003 Sep; 170(3): 1027–31.
Kim YT, Kyung Kim D, 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 Sep; 36(3): 391–3.
Rodríguez LV, Chen S, Jack GS. New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency. 2005; 288: 7.
Rahn DD, Acevedo JF, Word RA. Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse. Am J Physiol-Regul Integr Comp Physiol. 2008 Oct; 295(4): R1351–8.
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 Feb 1; 14(1): 31–7.
Furuta A, Jankowski RJ, Honda M, Pruchnic R, Yoshimura N, Chancellor MB. State of the art of where we are at using stem cells for stress urinary incontinence. Neurourol Urodyn. 2007 Nov; 26(7): 966–71.
Rodriguez LV, Alfonso Z, Zhang R, Leung J, Wu B, Ignarro LJ. Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells. Proc Natl Acad Sci. 2006 Aug 8; 103(32): 12167–72.
Pan HQ, Kerns JM, Lin DL, Liu S, Esparza N, Damaser MS. Increased duration of simulated childbirth injuries results in increased time to recovery. Am J Physiol-Regul Integr Comp Physiol. 2007 Apr; 292(4): R1738–44.
Cannon TW, Wojcik EM, Ferguson CL, Saraga S, Thomas C, Damaser MS. Effects of vaginal distension on urethral anatomy and function: Urethral Anatomy And Function After Vaginal Distension. BJU Int. 2002 Aug 14; 90(4): 403–7.
Lin C-S, Xin Z-C, Deng C-H, Ning H, Lin G, Lue TF. Recent advances in andrology-related stem cell research. Asian J Androl. 2008; 10(2): 171–5.
Sugino Y, Kanematsu A, Hayashi Y, Haga H, Yoshimura N, Yoshimura K, et al. Voided stain on paper method for analysis of mouse urination. Neurourol Urodyn. 2008 Aug; 27(6): 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 Pelvic Floor Dysfunct. 1998 Apr; 9(2): 88–93.
Almeida FG, Nobre YTD, Leite KR, Bruschini H. Autologous transplantation of adult adipose derived stem cells into rabbit urethral wall. Int Urogynecology J. 2010 Jun; 21(6): 743–8.
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies. Tissue Eng. 2001 Apr; 7(2): 211–28.
Yamamoto N, Akamatsu H, Hasegawa S, Yamada T, Nakata S, Ohkuma M, et al. Isolation of multipotent stem cells from mouse adipose tissue. J Dermatol Sci. 2007 Oct; 48(1): 43–52.
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 Jan; 59(1): 155–63.
Ni J, Li H, Zhou Y, Gu B, Xu Y, Fu Q, et al. Therapeutic Potential of Human Adipose-Derived Stem Cell Exosomes in Stress Urinary Incontinence – An in Vitro and in Vivo Study. Cell Physiol Biochem. 2018; 48(4): 1710–22.
Hart ML, Izeta A, Herrera-Imbroda B, Amend B, Brinchmann JE. Cell Therapy for Stress Urinary Incontinence. Tissue Eng Part B Rev. 2015 Aug; 21(4): 365–76.
Jack GS, Almeida FG, Zhang R, Alfonso ZC, Zuk PA, Rodríguez LV. Processed Lipoaspirate Cells For Tissue Engineering Of The Lower Urinary Tract: Implications For The Treatment Of Stress Urinary Incontinence And Bladder Reconstruction. J Urol. 2005 Nov; 174(5): 2041–5.
Si Z, Wang X, Sun C, Kang Y, Xu J, Wang X, et al. Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies. Biomed Pharmacother. 2019 Jun; 114: 108765.
Aufderklamm S, Aicher WK, Amend B, Stenzl A. Stress urinary incontinence and regenerative medicine: is injecting functional cells into the urethra feasible based on current knowledge and future prospects? Curr Opin Urol. 2019 Jul; 29(4): 394–9.
Mirotsou M, Jayawardena TM, Schmeckpeper J, Gnecchi M, Dzau VJ. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol. 2011 Feb; 50(2): 280–9.
Cardozo L. Neurobiology of stress urinary incontinence: New insights and implications for treatment. J Obstet Gynaecol. 2005 Jan; 25(6): 539–43.
Falconer C, Ekman-Ordeberg G, Hilliges M, Johansson O. Decreased innervation of the paraurethral epithelium in stress urinary incontinent women. Eur J Obstet Gynecol Reprod Biol. 1997 Apr; 72(2): 195–8.