Abstract
Objective
Stress urinary incontinence (SUI) remains a prevalent condition with substantial economic and quality-of-life impact. Treatment for incontinence historically culminates with invasive surgical procedures with recognized complication profiles. Innovative directions for SUI therapeutics are on the horizon, including the utilization of adult autologous muscle-derived cells for urinary sphincter regeneration (AMDC-USR). Herein, we visit fundamental concepts of innovative regenerative medicine technologies for urologic applications.
Methods
Synopsis of contemporary literature review regarding adult autologous muscle-derived cells for urinary sphincter regeneration is presented.
Results
Current published literature presents safety and efficacy data regarding AMDC-USR injection in 80 patients at 12-month follow-up. In these early studies, no long-term adverse events were reported and patients undergoing cellular injection at higher doses revealed at least 50% reduction in stress leaks and pad weight at 12-month follow-up. All dose groups demonstrated statistically significant improvement in patient-reported incontinence-specific quality-of-life scores at 12-month follow-up. Conclusions from the pooled analyses indicate that injection of AMDC-USR across a range of dosages appears safe. Efficacy data suggest a dose response with more patients responsive to the higher doses of AMDC-USR.
Conclusion
Applications for utilization of autologous cellular therapies for treatment of SUI, and conceivably multiple additional indications, are approaching realization. Multiple Phase III randomized, placebo-controlled studies for AMDC-USR are concluding or ongoing to launch this regenerative option for the millions of patients who may ultimately benefit.
Similar content being viewed by others
References
Reynolds WS, Dmochowski RR, Penson DF (2011) Epidemiology of stress urinary incontinence in women. Curr Urol Rep 12(5):370–376
Norton P, Brubaker L (2006) Urinary incontinence in women. Lancet 367(9504):57–67
Danforth KN, Townsend MK, Lifford K, Curhan GC, Resnick NM, Grodstein F (2006) Risk factors for urinary incontinence among middle-aged women. Am J Obstet Gynecol 194(2):339–345
Petros PE, Woodman PJ (2008) The integral theory of continence. Int Urogynecol J Pelvic Floor Dysfunct 19(1):35–40
Gill BC, Damaser MS, Vasavada SP, Goldman HB (2013) Stress incontinence in the era of regenerative medicine: reviewing the importance of the pudendal nerve. J Urol. 190(1):22–28
Thompson I, Kaufman MR (2010) Nonsurgical interventions for incontinence: where is the evidence? Curr Blad Dysfn Rep 5(3):163–167
Kobashi KC, Albo ME, Dmochowski RR, Ginsberg DA, Goldman HB, Gomelsky A et al (2017) Surgical treatment of female stress urinary incontinence: AUA/SUFU guideline. J Urol 198(4):875–883
Wood LN, Anger JT (2014) Urinary incontinence in women. BMJ 349:g4531
SUFU. https://sufuorg.com/docs/news/augs-sufu-mus-position-statement.aspx
Koski ME, Chamberlain J, Rosoff J, Vaughan T, Kaufman MR, Winters JC et al (2014) Patient perception of transvaginal mesh and the media. Urology 84(3):575–582
Athanasopoulos A, Gyftopoulos K, McGuire EJ (2011) Efficacy and preoperative prognostic factors of autologous fascia rectus sling for treatment of female stress urinary incontinence. Urology 78(5):1034–1038
Williams JK, Dean A, Badlani G, Andersson KE (2016) Regenerative medicine therapies for stress urinary incontinence. J Urol 196(6):1619–1626
Aragon IM, Imbroda BH, Lara MF (2018) Cell therapy clinical trials for stress urinary incontinence: current status and perspectives. Int J Med Sci 15(3):195–204
Zambon JP, Williams KJ, Bennington J, Badlani GH (2019) Applicability of regenerative medicine and tissue engineering for the treatment of stress urinary incontinence in female patients. Neurourol Urodyn 38(Suppl 4):S76–S83
Hwang K, Lewis S, Lamb DJ (2010) Stem cell research: implications for urology. AUA Upd Ser 29(8):77–84
Vinarov A, Atala A, Yoo J, Slusarenco R, Zhumataev M, Zhito A et al (2018) Cell therapy for stress urinary incontinence: present-day frontiers. J Tissue Eng Regen Med 12(2):e1108–e1121
Sun DZ, Abelson B, Babbar P, Damaser MS (2019) Harnessing the mesenchymal stem cell secretome for regenerative urology. Nat Rev Urol 16(6):363–375
Wang HJ, Chuang YC, Chancellor MB (2011) Development of cellular therapy for the treatment of stress urinary incontinence. Int Urogynecol J 22(9):1075–1083
Chancellor MB, Yokoyama T, Tirney S, Mattes CE, Ozawa H, Yoshimura N et al (2000) 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 19(3):279–287
Bennington J, Williams JK, Andersson KE (2019) New concepts in regenerative medicine approaches to the treatment of female stress urinary incontinence. Curr Opin Urol 29(4):380–384
Yokoyama T, Yoshimura N, Dhir R, Qu Z, Fraser MO, Kumon H et al (2001) Persistence and survival of autologous muscle derived cells versus bovine collagen as potential treatment of stress urinary incontinence. J Urol 165(1):271–276
Furuta A, Jankowski RJ, Pruchnic R, Yoshimura N, Chancellor MB (2007) The promise of stem cell therapy to restore urethral sphincter function. Curr Urol Rep 8(5):373–378
Kwon D, Kim Y, Pruchnic R, Jankowski R, Usiene I, de Miguel F et al (2006) 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 68(2):449–454
Yiou R, Yoo JJ, Atala A (2003) Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts. Transplantation 76(7):1053–1060
Yokoyama T, Pruchnic R, Lee JY, Chuang YC, Jumon H, Yoshimura N et al (2001) Autologous primary muscle-derived cells transfer into the lower urinary tract. Tissue Eng 7(4):395–404
Chermansky CJ, Tarin T, Kwon DD, Jankowski RJ, Cannon TW, de Groat WC et al (2004) Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency. Urology 63(4):780–785
Cannon TW, Lee JY, Somogyi G, Pruchnic R, Smith CP, Huard J et al (2003) Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra. Urology 62(5):958–963
Lee JY, Cannon TW, Pruchnic R, Fraser MO, Huard J, Chancellor MB (2003) 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 14(1):31–37 (discussion 7)
Kleinert S, Horton R (2008) Retraction–autologous myoblasts and fibroblasts versus collagen [corrected] for treatment of stress urinary incontinence in women: a [corrected] randomised controlled trial. Lancet 372(9641):789–790
Carr LK, Steele D, Steele S, Wagner D, Pruchnic R, Jankowski R et al (2008) 1-year follow-up of autologous muscle-derived stem cell injection pilot study to treat stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 19(6):881–883
Carr LK, Robert M, Kultgen PL, Herschorn S, Birch C, Murphy M et al (2013) Autologous muscle derived cell therapy for stress urinary incontinence: a prospective, dose ranging study. J Urol 189(2):595–601
Peters KM, Dmochowski RR, Carr LK, Robert M, Kaufman MR, Sirls LT et al (2014) Autologous muscle derived cells for treatment of stress urinary incontinence in women. J Urol 192(2):469–476
Carr L, Tu LM, Robert M, Quinlan D, Carlson K, Herschorn S, Dmochowski R, Peters K, Kaufman M, Jankowski R, Chancellor M (ed) (2017) Autologous muscle derived cells for urinary sphincter repair for recurrent or persistent stress urinary incontinence after continence surgery. In: AUA annual meeting; 2017; Boston, MA
Pruchnic RJR, Kaufman MR (ed) (2017) Lessons learned from a multicenter, randomized, double-blind, placebo controlled study of autologous muscle derived cells for urinary sphincter repair. In: International continence society annual meeting; 2017; Florence, Italy
Quinlan D, Carr L, Tu LM, Robert M, Carlson K, Herschorn S, Dmochowski R, Peters K, Kaufman M, Jankowski R, Chancellor M (ed) (2017) Autologous muscle derived cells for urinary sphincter repair for recurrent or persistent stress urinary incontinence after continence surgery. In: IUGA; 2017; Vancouver, Canada
Blaganje M, Lukanovic A (2012) Intrasphincteric autologous myoblast injections with electrical stimulation for stress urinary incontinence. Int J Gynaecol Obstet 117(2):164–167
Blaganje M, Lukanovic A (2013) Ultrasound-guided autologous myoblast injections into the extrinsic urethral sphincter: tissue engineering for the treatment of stress urinary incontinence. Int Urogynecol J 24(4):533–535
Sebe P, Doucet C, Cornu JN, Ciofu C, Costa P, de Medina SG et al (2011) Intrasphincteric injections of autologous muscular cells in women with refractory stress urinary incontinence: a prospective study. Int Urogynecol J 22(2):183–189
Elmi A, Kajbafzadeh AM, Tourchi A, Talab SS, Esfahani SA (2011) Safety, efficacy and health related quality of life of autologous myoblast transplantation for treatment of urinary incontinence in children with bladder exstrophy-epispadias complex. J Urol 186(5):2021–2026
Stangel-Wojcikiewicz K, Jarocha D, Piwowar M, Jach R, Uhl T, Basta A et al (2014) Autologous muscle-derived cells for the treatment of female stress urinary incontinence: a 2-year follow-up of a Polish investigation. Neurourol Urodyn 33(3):324–330
Gras S, Klarskov N, Lose G (2014) Intraurethral injection of autologous minced skeletal muscle: a simple surgical treatment for stress urinary incontinence. J Urol 192(3):850–855
Gerullis H, Eimer C, Georgas E, Homburger M, El-Baz AG, Wishahi M et al (2012) Muscle-derived cells for treatment of iatrogenic sphincter damage and urinary incontinence in men. Sci World J 2012:898535
Levanovich PE, Diokno A, Hasenau DL, Lajiness M, Pruchnic R, Chancellor MB (2015) Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. Int Urol Nephrol 47(3):465–467
Author information
Authors and Affiliations
Contributions
MRK: Manuscript writing/editing.
Corresponding author
Ethics declarations
Conflict of interest
MR Kaufman serves as Global Principal Investigator for Cook Myosite, Inc.
Research involving human participants and/or animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed in the reviewed studies. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee for the reviewed articles and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the included studies.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kaufman, M.R. Contemporary application of autologous muscle-derived cells for urinary sphincter regeneration. World J Urol 38, 2095–2099 (2020). https://doi.org/10.1007/s00345-019-03018-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00345-019-03018-9