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  • Review Article
  • Published:

Cell-based secondary prevention of childbirth-induced pelvic floor trauma

Nature Reviews Urology volume 14, pages 373–385 (2017)Cite this article

Subjects

Key Points

  • The aetiology and pathophysiology of pelvic-floor dysfunction (PFD) is incompletely understood, although pregnancy, and vaginal birth in particular, cause damage that seems to be insufficiently repaired in some women

  • After nerve and muscle trauma, endogenous repair processes are initiated, but these mechanisms often fail to completely repair the original damage

  • Administration of exogenous drugs, growth factors, cells or even tissue might improve the function of innate repair mechanisms

  • In small-animal models of PFD, the concept of administration of mesenchymal stem cells or factors secreted by these cells has positive effects on pelvic-floor function

  • Clinical trials in patients with either urinary incontinence or faecal incontinence have provided both subjective improvements and objective documentation of improved pelvic floor function after autologous mesenchymal stem cell administration

  • Intuitively, better outcomes seem likely when stem cells are given around the trauma period, before trauma-induced damage becomes a clinical reality; preclinical data are required to support this hypothesis

Abstract

With advancing population age, pelvic-floor dysfunction (PFD) will affect an increasing number of women. Many of these women wish to maintain active lifestyles, indicating an urgent need for effective strategies to treat or, preferably, prevent the occurrence of PFD. Childbirth and pregnancy have both long been recognized as crucial contributing factors in the pathophysiology of PFD. Vaginal delivery of a child is a serious traumatic event, causing anatomical and functional changes in the pelvic floor. Similar changes to those experienced during childbirth can be found in symptomatic women, often many years after delivery. Thus, women with such PFD symptoms might have incompletely recovered from the trauma caused by vaginal delivery. This hypothesis creates the possibility that preventive measures can be initiated around the time of delivery. Secondary prevention has been shown to be beneficial in patients with many other chronic conditions. The current general consensus is that clinicians should aim to minimize the extent of damage during delivery, and aim to optimize healing processes after delivery, therefore preventing later dysfunction. A substantial amount of research investigating the potential of stem-cell injections as a therapeutic strategy for achieving this purpose is currently ongoing. Data from small animal models have demonstrated positive effects of mesenchymal stem-cell injections on the healing process following simulated vaginal birth injury.

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Figure 1: A generalized time course of changes in myeloid cell populations and in the expression of muscle-specific transcription factors, enzymes, and structural proteins in muscle following acute muscle injury.
Figure 2: Cellular responses to peripheral nerve injury.
Figure 3: Simplified representation of the interactions between mesenchymal stem cells, the immune system and regenerating muscle.

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Authors and Affiliations

  1. Department of Development and Regeneration, Cluster Organ Systems, Faculty of Medicine, University of Leuven, Herestraat 49, Leuven, 3000, Belgium

    Geertje Callewaert, Marina Monteiro Carvalho Mori Da Cunha, Nikhil Sindhwani, Maarten Albersen & Jan Deprest

  2. Department of Obstetrics and Gynaecology, Division Woman and Child, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium

    Geertje Callewaert, Maurilio Sampaolesi & Jan Deprest

  3. Department of Urology, University Hospitals Leuven, Herestraat 49, Leuven, 3000, Belgium

    Maarten Albersen

Authors
  1. Geertje Callewaert
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  2. Marina Monteiro Carvalho Mori Da Cunha
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  3. Nikhil Sindhwani
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  4. Maurilio Sampaolesi
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  5. Maarten Albersen
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  6. Jan Deprest
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Contributions

G.C. and N.S. researched data for this article, G.C., M.S., M.A. and J.D. made a substantial contribution to discussions of content, G.C., M.M.C.M.d.C., N.S., M.A. and J.D. wrote the manuscript and all authors reviewed and/or edited the manuscript before submission.

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Correspondence to Jan Deprest.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information S2 (table)

Use of mesenchymal stem cells in rat model of simulated vaginal birth injury (DOC 205 kb)

Trauma to the levator ani muscle during childbirth

Exposure of the levator ani to excessive forces during childbirth, which substantially increase the risk of pelvic-floor dysfunctions. (MP4 4656 kb)

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Callewaert, G., Da Cunha, M., Sindhwani, N. et al. Cell-based secondary prevention of childbirth-induced pelvic floor trauma. Nat Rev Urol 14, 373–385 (2017). https://doi.org/10.1038/nrurol.2017.42

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