Regenerative medicine and injection therapies in stress urinary incontinence

Abstract

Stress urinary incontinence (SUI) is a common and bothersome condition. Anti-incontinence surgery has high cure rates, but concerns about mesh tapes have resulted in the resurgence of surgical procedures that involve increased abdominopelvic dissection and morbidity. Injection therapy with urethral bulking agents or stem cell formulations have been developed as minimally invasive alternatives. Many synthetic and biological bulking agents have been trialled, but several have been discontinued owing to safety concerns. The use of Macroplastique and Contigen has the largest evidence base, but, overall, success rates seem to be similar between the various agents and positive outcomes are poorly sustained for more than 6 months. Furthermore, subjective cure rates, although initially high, also deteriorate over time. The available data consistently demonstrate manifestly poorer outcomes for injection therapies than for surgery. Stem cell treatments are thought to functionally regenerate the urethral sphincter in patients with suspected intrinsic sphincter deficiency. Autologous adipose and muscle-derived stem cells seem to be the intuitive cell source, as they are comparatively abundant, can be harvested and cause minimal donor site morbidity. To date, only a few small clinical studies have been reported and most data are derived from animal models. The success rates of stem cell injection therapies seem to be comparable with those of bulking agents.

Key points

  • An increasing number of bulking procedures are being performed with objective cure rates that are inferior to those of open surgery, but their minimally invasive application is an attractive prospect.

  • The rates of subjective improvements for bulking agent therapies are high, but these treatments should not be offered to patients who seek a permanent cure of their stress urinary incontinence.

  • Stem cells derived from muscle or fat are the most commonly studied cells for use as a regenerative injection therapy.

  • Harvest and injection of stem cells seem not to have high rates of morbidity, and the outcomes of stem cell injections seem to be better maintained at 12 months than those of bulking agents.

  • Studies of labelled-cell injections to enable tracking demonstrate low stem cell proportions in the sphincter by 12 months; hence, paracrine effects of the cellular concentrate might be as important as the cells themselves.

  • The development of stem cell therapies is limited to preclinical and human feasibility studies, owing to the difficulty of assessing injected cell fate; thus, outcome measurements are limited to subjective and objective cure rates.

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Fig. 1: Neural control of the female lower urinary tract and the structure of the female urethra.
Fig. 2: Application of urethral bulking agents.

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Acknowledgements

C.J.H., S.M., W.K.A., A.S. and C.R.C are members of the Regenerative Sphincter Therapy (ReST) Consortium funded by the European Cooperation in Science and Technology (COST).

Review criteria

A search of the PubMed and Scopus databases was performed to identify articles published between 1995 and May 2018 using the following search terms: “bulking agent”, “urethral injection”, “regenerative medicine” and “stem cell injection”. Results were limited to “stress urinary incontinence”. All available randomized controlled trials, cohort studies and case series were included in this narrative review.

Author information

C.J.H. and S.R. researched data for the article. All authors made substantial contributions to the discussion of content and wrote the manuscript. C.J.H., S.M., W.K.A., A.S. and C.R.C. reviewed and/or edited the manuscript before submission.

Correspondence to Christopher J. Hillary.

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Hillary, C.J., Roman, S., MacNeil, S. et al. Regenerative medicine and injection therapies in stress urinary incontinence. Nat Rev Urol (2020). https://doi.org/10.1038/s41585-019-0273-4

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