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Regenerative medicine for anal incontinence: a review of regenerative therapies beyond cells

Abstract

Introduction and hypothesis

Current treatment modalities for anal sphincter injuries are ineffective for many patients, prompting research into restorative and regenerative therapies. Although cellular therapy with stem cells and progenitor cells show promise in animal models with short-term improvement, there are additional regenerative approaches that can augment or replace cellular therapies for anal sphincter injuries. The purpose of this article is to review the current knowledge of cellular therapies for anal sphincter injuries and discusses the use of other regenerative therapies including cytokine therapy with CXCL12.

Methods

A literature search was performed to search for articles on cellular therapy and cytokine therapy for anal sphincter injuries and anal incontinence.

Results

The article search identified 337 articles from which 33 articles were included. An additional 12 referenced articles were included as well as 23 articles providing background information. Cellular therapy has shown positive results for treating anal sphincter injuries and anal incontinence in vitro and in one clinical trial. However, cellular therapy has disadvantages such as the source and processing of stem cells and progenitor cells. CXCL12 does not have such issues while showing promising in vitro results for treating anal sphincter injuries. Additionally, electrical stimulation and extracorporeal shock wave therapy are potential regenerative medicine adjuncts for anal sphincter injuries. A vision for future research and clinical applications of regenerative medicine for anal sphincter deficiencies is provided.

Conclusion

There are viable regenerative medicine therapies for anal sphincter injuries beyond cellular therapy. CXCL12 shows promise as a focus of therapeutic research in this field.

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Abbreviations

OASI:

obstetrical anal sphincter injury

SDF-1:

stromal-derived factor 1

IM:

intramuscular

IV:

intravenous

GFP:

green fluorescent protein

ISD:

intrinsic sphincter deficiency

ESWT:

extracorporeal shock wave therapy

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Acknowledgements

Janine Tillett MSLS AHIP from the Wake Forest School of Medicine Carpenter Library was instrumental in performing the academic article searches for this article.

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Authors

Contributions

Andre Plair: Protocol/project development, data collection, manuscript writing.

Julie Bennington: Manuscript editing.

James Koudy Williams: Manuscript editing.

Candace Parker-Autry: Manuscript editing.

Catherine Ann Matthews: Protocol/project development, manuscript editing.

Gopal Badlani: Protocol/project development, manuscript editing.

Corresponding author

Correspondence to Andre Plair.

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Conflict of interest

Andre Plair, grant support from Neomedic.

Julie Bennington, supported by NIH Post-doctoral T32 Institutional Training Grant “Laboratory Animal and Comparative Medicine Research” (NIH T32 OD010957).

James Koudy Williams, None.

Candace Parker-Autry, None.

Catherine Ann Matthews, consultant for Boston Scientific and Pelvalon; grant support from Boston Scientific and Neomedic; expert defense for Johnson and Johnson.

Gopal Badlani, advisory panelist for Olympus and Neotract; board of directors of AAGUS, and Urology Care Foundation.

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Plair, A., Bennington, J., Williams, J.K. et al. Regenerative medicine for anal incontinence: a review of regenerative therapies beyond cells. Int Urogynecol J 32, 2337–2347 (2021). https://doi.org/10.1007/s00192-020-04620-x

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Keywords

  • Regenerative medicine
  • Fecal incontinence
  • Stem cells
  • Cytokines
  • CXCL12
  • Anal sphincter injuries