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Developing Engineered Biosphincters to Cure Fecal Incontinence

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Review of “Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3-Month Follow-Up Study” from STEM CELLS Translational Medicine by Stuart P. Atkinson

An estimated 8.3% of U.S. adults [1] lose anal sphincter function due to aging, trauma, anorectal surgery, or medical comorbidity [2, 3] leading to the devastating clinical condition of fecal incontinence (FI). The lack of effective treatment options prompted researchers from the laboratory of Khalil N. Bitar (Wake Forest Institute for Regenerative Medicine, North Carolina, USA) to engineer innervatable biosphincters from smooth muscle cells and enteric neural progenitor cells which they successfully transplanted into rodents [4, 5]. Now, the team returns with a new study in which they move to a large animal model (rabbit) to test the efficacy of their autologous engineered biosphincters as a treatment for FI [6].

Bohl et al. employed an experimental injury to the rabbit internal anal sphincter (IAS) to mimic FI and measured sphincter function up to three months post transplantation. Encouragingly, while non-treated rabbits displayed a sustained loss of sphincter function over three months, transplantation of the engineered biosphincters led to the restoration of sphincter function. This success correlated to the restoration of smooth muscle reconstruction and continuity, as measured histologically.

Overall, the authors suggest that their data confirms the rabbit as a reproducible and reliable animal model of passive human FI and underlines the exciting potential of their engineered biosphincter strategy. Further studies aim to extend follow up times and expand animal numbers to confirm the effective and efficient restoration of anal sphincter function before moving to human clinical trials.

Stay tuned to the Stem Cells Portal to find out more on this encouraging treatment option!

References

  1. Whitehead WE, Borrud L, Goode PS, et al. Fecal incontinence in US adults: epidemiology and risk factors. Gastroenterology 2009;137:512-517, 517 e511-512.
  2. Huebner M, Margulies RU, Fenner DE, et al. Age effects on internal anal sphincter thickness and diameter in nulliparous females. Dis Colon Rectum 2007;50:1405-1411.
  3. Lindsey I, Jones OM, Smilgin-Humphreys MM, et al. Patterns of fecal incontinence after anal surgery. Dis Colon Rectum 2004;47:1643-1649.
  4. Gilmont RR, Raghavan S, Somara S, et al. Bioengineering of physiologically functional intrinsically innervated human internal anal sphincter constructs. Tissue Eng Part A 2014;20:1603-1611.
  5. Raghavan S, Miyasaka EA, Gilmont RR, et al. Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells. Surgery 2014;155:668-674.
  6. Bohl JL, Zakhem E, and Bitar KN. Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3-Month Follow-Up Study. STEM CELLS Translational Medicine 2017;6:1795-1802.