The primary objective was to evaluate the effect of autologous muscle-derived cell (AMDC) injections on the urethral sphincter morphometry compared to placebo injections. Secondary aims were to explore the reduction of stress incontinence episode frequency (IEF) and factors associated with the efficacy of AMDC.
This prospective randomized-controlled study compared the urethral sphincter volumes of participants who had received either an intra-sphincteric injection of 4 cc AMDC in injection media or 4 cc placebo solution, using a transperineal 3D/4D ultrasound at baseline and at 12 months. The reduction of stress IEF on 3-day bladder diary and potential predictors at baseline for response to AMDC were assessed.
Fifty-eight participants were included in the study. Compared to baseline, the mean total and external sphincter volumes increased significantly in both groups (respectively, p = 0.001 and p < 0.001 in the AMDC group, p < 0.001 and p = 0.005 in the placebo group) at 12 months. Both groups showed a significant reduction of stress IEF compared to baseline (p = 0.03 and p ≤ 0.001 for AMDC and placebo groups, respectively). There were no between-group differences regarding total and external sphincter volumes and reduction of stress IEF. A longer urethral length (p ≤ 0.001) and a larger external sphincter volume (p ≤ 0.05) were significantly associated with lower stress IEF.
Significant increases of sphincter volumes as well as reduction of stress IEF occurred among the AMDC and placebo injection groups with no between-group differences at 12 months. A longer urethral length and a larger external sphincter volume at baseline were identified as potential predictors of AMDC injection response.
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Bettez M, Tu LM, Carlson K et al (2012) 2012 Update: guidelines for adult urinary incontinence collaborative consensus document for the Canadian Urological Association. Can Urol Assoc J 6:354–363
Schauer I, Bock H, Eredics K et al (2016) 10 years follow-up after mid-urethral sling implantation: high rate of cure yet a re-occurrence of OAB-symptoms. Neurourol Urodyn 36:614–619. https://doi.org/10.1002/nau.22972
Leone Roberti Maggiore U, Bogani G, Meschia M et al (2015) Urethral bulking agents versus other surgical procedures for the treatment of female stress urinary incontinence: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 189:48–54. https://doi.org/10.1016/j.ejogrb.2015.03.025
Gill BC, Sun DZ, Damaser MS (2018) Stem cells for urinary incontinence: functional differentiation or cytokine effects? Urology 117:9–17. https://doi.org/10.1016/j.urology.2018.01.002
Nikolavasky D, Stangel-Wojcikiewicz K, Stec M, Chancellor MB (2011) Stem cell therapy: a future treatment of stress urinary incontinence. Semin Reprod Med 29:61–70. https://doi.org/10.1055/s-0030-1268705
Oliveira FR, Ramos JGL, Martins-Costa S (2006) Translabial ultrasonography in the assessment of urethral diameter and intrinsic urethral sphincter deficiency. J Ultrasound Med Off J Am Inst Ultrasound Med 25:1153–1158; quiz 1159–1160
Jankowski RJ, Tu LM, Carlson C et al (2018) A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence. Int Urol Nephrol 50:2153–2165. https://doi.org/10.1007/s11255-018-2005-8
Dietz HP (2010) Pelvic floor ultrasound: a review. Am J Obstet Gynecol 202:321–334. https://doi.org/10.1016/j.ajog.2009.08.018
Siafarikas F, Staer-Jensen J, Braekken IH et al (2013) Learning process for performing and analyzing 3D/4D transperineal ultrasound imaging and interobserver reliability study. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 41:312–317. https://doi.org/10.1002/uog.11192
Braekken IH, Majida M, Engh ME, Bø K (2009) Test–retest reliability of pelvic floor muscle contraction measured by 4D ultrasound. Neurourol Urodyn 28:68–73. https://doi.org/10.1002/nau.20618
Majida M, Braekken IH, Umek W et al (2009) Interobserver repeatability of three- and four-dimensional transperineal ultrasound assessment of pelvic floor muscle anatomy and function. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 33:567–573. https://doi.org/10.1002/uog.6351
Duckett J, Patil A, Aggarwal I (2008) The effect of duloxetine on urethral sphincter morphology. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 31:206–209. https://doi.org/10.1002/uog.5202
Isom-Batz G, Zimmern PE (2009) Collagen injection for female urinary incontinence after urethral or periurethral surgery. J Urol 181:701–704. https://doi.org/10.1016/j.juro.2008.10.027
Abrams P, Cardozo L, Wagg A, Wein AJ (2016) Incontinence 6th Edition 2017, 6th edn. ICUD-ICS, Tokyo
Athanasiou S, Khullar V, Boos K et al (1999) Imaging the urethral sphincter with three-dimensional ultrasound. Obstet Gynecol 94:295–301
Madill SJ, Pontbriand-Drolet S, Tang A, Dumoulin C (2015) Changes in urethral sphincter size following rehabilitation in older women with stress urinary incontinence. Int Urogynecol J 26:277–283. https://doi.org/10.1007/s00192-014-2507-6
Turco MP, de Souza AB, de Campos SI et al (2017) Periurethral muscle-derived mononuclear cell injection improves urethral sphincter restoration in rats. Neurourol Urodyn 36:2011–2018. https://doi.org/10.1002/nau.23262
Dissaranan C, Cruz MA, Kiedrowski MJ et al (2014) Rat mesenchymal stem cell secretome promotes elastogenesis and facilitates recovery from simulated childbirth injury. Cell Transpl 23:1395–1406. https://doi.org/10.3727/096368913X670921
Sadeghi Z, Isariyawongse J, Kavran M et al (2016) Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution. Int Urogynecol J 27:291–300. https://doi.org/10.1007/s00192-015-2831-5
Sinha S, Sinha U, Malis V et al (2018) Exploration of male urethral sphincter complex using diffusion tensor imaging (DTI)-based fiber-tracking. J Magn Reson Imaging JMRI 48:1002–1011. https://doi.org/10.1002/jmri.26017
Aust MC, Reimers K, Kaplan HM et al (2011) Percutaneous collagen induction–regeneration in place of cicatrisation? J Plast Reconstr Aesthetic Surg JPRAS 64:97–107. https://doi.org/10.1016/j.bjps.2010.03.038
APTA Public Policy, Practice, and Professional Affairs Unit (2013) Description of dry needling in clinical practice: an education resource paper, page 2.
Cross KM, McMurray M (2017) Dry needling increases muscle thickness in a subject with persistent muscle dysfunction: a case report. Int J Sports Phys Ther 12:468–475
Aref-Adib M, Lamb BW, Lee HB et al (2013) Stem cell therapy for stress urinary incontinence: a systematic review in human subjects. Arch Gynecol Obstet 288:1213–1221. https://doi.org/10.1007/s00404-013-3028-0
Blaganje M, Lukanović A (2012) Intrasphincteric autologous myoblast injections with electrical stimulation for stress urinary incontinence. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet 117:164–167. https://doi.org/10.1016/j.ijgo.2011.11.029
Mungovan SF, Sandhu JS, Akin O et al (2017) Preoperative membranous urethral length measurement and continence recovery following radical prostatectomy: a systematic review and meta-analysis. Eur Urol 71:368–378. https://doi.org/10.1016/j.eururo.2016.06.023
Cassadó Garriga J, Pessarrodona Isern A, Rodríguez Carballeira M et al (2017) Three-dimensional translabial ultrasound assessment of urethral supports and the urethral sphincter complex in stress urinary incontinence. Neurourol Urodyn 36:1839–1845. https://doi.org/10.1002/nau.23193
Morgan DM, Umek W, Guire K et al (2009) Urethral sphincter morphology and function with and without stress incontinence. J Urol 182:203–209. https://doi.org/10.1016/j.juro.2009.02.129
This research and infrastructure were funded by Cook Myosite and the Canadian Foundation for Innovation, respectively. Dr. Mélanie Morin is supported by a research salary award from the Fonds de la recherche du Québec—Santé. The authors wish to acknowledge the involvement of physiotherapy students (C. Mitterer, G. Jeanotte Maranda, M. Gervais-Mercier, K. Langelier, and L. Lapierre) in the development of ultrasound data analysis. The authors also thank Marie-Pierre Garant (Unité clinique et épidémiologique from the research center of the CHUS) for her advice on statistical analysis.
This research and infrastructure were funded by Cook Myosite and the Canadian Foundation for Innovation, respectively. Dr. Mélanie Morin is supported by a research salary award from the Fonds de la recherche du Québec—Santé.
Conflicts of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution (Comité d’éthique de la recherche en santé chez l’humain du CHUS et de l’Université de Sherbrooke, reference number not applicable) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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Ismail, S., Morin, M. & Tu, L.M. Assessment of the effects of autologous muscle-derived cell injections on urethral sphincter morphometry using 3D/4D ultrasound. World J Urol 38, 2881–2889 (2020). https://doi.org/10.1007/s00345-020-03076-4
- Stress urinary incontinence
- Muscle cells
- Cell therapy