Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3-Month Follow-Up Study

Overview

Journal Stem Cells Transl Med

Publisher Oxford University Press

Specialties Cell Biology
Pharmacology

Date 2017 Jul 6

PMID 28678378

Citations 7

Authors

Jaime L Bohl

Elie Zakhem

Khalil N Bitar

Affiliations

Soon will be listed here.

Abstract

Fecal incontinence (FI) is the involuntary passage of fecal material. Current treatments have limited successful outcomes. The objective of this study was to develop a large animal model of passive FI and to demonstrate sustained restoration of fecal continence using anorectal manometry in this model after implantation of engineered autologous internal anal sphincter (IAS) biosphincters. Twenty female rabbits were used in this study. The animals were divided into three groups: (a) Non-treated group: Rabbits underwent IAS injury by hemi-sphincterectomy without treatment. (b) Treated group: Rabbits underwent IAS injury by hemi-sphincterectomy followed by implantation of autologous biosphincters. (c) Sham group: Rabbits underwent IAS injury by hemi-sphincterectomy followed by re-accessing the surgical site followed by immediate closure without implantation of biosphincters. Anorectal manometry was used to measure resting anal pressure and recto-anal inhibitory reflex (RAIR) at baseline, 1 month post-sphincterectomy, up to 3 months after implantation and post-sham. Following sphincterectomy, all rabbits had decreased basal tone and loss of RAIR, indicative of FI. Anal hygiene was also lost in the rabbits. Decreases in basal tone and RAIR were sustained more than 3 months in the non-treated group. Autologous biosphincters were successfully implanted into eight donor rabbits in the treated group. Basal tone and RAIR were restored at 3 months following biosphincter implantation and were significantly higher compared with rabbits in the non-treated and sham groups. Histologically, smooth muscle reconstruction and continuity was restored in the treated group compared with the non-treated group. Results in this study provided promising outcomes for treatment of FI. Results demonstrated the feasibility of developing and validating a large animal model of passive FI. This study also showed the efficacy of the engineered biosphincters to restore fecal continence as demonstrated by manometry. Stem Cells Translational Medicine 2017;6:1795-1802.

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References

Huebner M, Margulies R, Fenner D, Ashton-Miller J, Bitar K, DeLancey J . Age effects on internal anal sphincter thickness and diameter in nulliparous females. Dis Colon Rectum. 2007; 50(9):1405-11. PMC: 2288793. DOI: 10.1007/s10350-006-0877-7. View

Rao S, Azpiroz F, Diamant N, Enck P, Tougas G, Wald A . Minimum standards of anorectal manometry. Neurogastroenterol Motil. 2002; 14(5):553-9. DOI: 10.1046/j.1365-2982.2002.00352.x. View

Salcedo L, Damaser M, Butler R, Jiang H, Hull T, Zutshi M . Long-term effects on pressure and electromyography in a rat model of anal sphincter injury. Dis Colon Rectum. 2010; 53(8):1209-17. DOI: 10.1007/DCR.0b013e3181de7fe0. View

Whitehead W, Borrud L, Goode P, Meikle S, Mueller E, Tuteja A . Fecal incontinence in US adults: epidemiology and risk factors. Gastroenterology. 2009; 137(2):512-7, 517.e1-2. PMC: 2748224. DOI: 10.1053/j.gastro.2009.04.054. View

Zutshi M, Salcedo L, Zaszczurynski P, Hull T, Butler R, Damaser M . Effects of sphincterotomy and pudendal nerve transection on the anal sphincter in a rat model. Dis Colon Rectum. 2009; 52(7):1321-9. DOI: 10.1007/DCR.0b013e31819f746d. View

Hong K, DaSilva G, Kalaskar S, Chong Y, Wexner S . Long-term outcomes of artificial bowel sphincter for fecal incontinence: a systematic review and meta-analysis. J Am Coll Surg. 2013; 217(4):718-25. DOI: 10.1016/j.jamcollsurg.2013.04.028. View

Oh H, Lee H, Lee J, Oh S, Lim J, Ahn S . Functional and histological evidence for the targeted therapy using biocompatible polycaprolactone beads and autologous myoblasts in a dog model of fecal incontinence. Dis Colon Rectum. 2015; 58(5):517-25. DOI: 10.1097/DCR.0000000000000346. View

Kang S, Lee H, Lim J, Oh S, Kim S, Hong S . Injection of porous polycaprolactone beads containing autologous myoblasts in a dog model of fecal incontinence. J Korean Surg Soc. 2013; 84(4):216-24. PMC: 3616275. DOI: 10.4174/jkss.2013.84.4.216. View

Montoya T, Acevedo J, Smith B, Keller P, Sailors J, Tang L . Myogenic stem cell-laden hydrogel scaffold in wound healing of the disrupted external anal sphincter. Int Urogynecol J. 2015; 26(6):893-904. DOI: 10.1007/s00192-014-2620-6. View

10.

Raghavan S, Miyasaka E, Gilmont R, Somara S, Teitelbaum D, Bitar K . Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells. Surgery. 2014; 155(4):668-74. PMC: 4017655. DOI: 10.1016/j.surg.2013.12.023. View

11.

Bartlett L, Nowak M, Ho Y . Impact of fecal incontinence on quality of life. World J Gastroenterol. 2009; 15(26):3276-82. PMC: 2710784. DOI: 10.3748/wjg.15.3276. View

12.

Kaur G, Gardiner A, Duthie G . Rectoanal reflex parameters in incontinence and constipation. Dis Colon Rectum. 2002; 45(7):928-33. DOI: 10.1007/s10350-004-6331-9. View

13.

Darnis B, Faucheron J, Damon H, Barth X . Technical and functional results of the artificial bowel sphincter for treatment of severe fecal incontinence: is there any benefit for the patient?. Dis Colon Rectum. 2013; 56(4):505-10. DOI: 10.1097/DCR.0b013e3182809490. View

14.

Gilmont R, Raghavan S, Somara S, Bitar K . Bioengineering of physiologically functional intrinsically innervated human internal anal sphincter constructs. Tissue Eng Part A. 2013; 20(11-12):1603-11. PMC: 4029137. DOI: 10.1089/ten.TEA.2013.0422. View

15.

Lindsey I, Jones O, Smilgin-Humphreys M, Cunningham C, Mortensen N . Patterns of fecal incontinence after anal surgery. Dis Colon Rectum. 2004; 47(10):1643-9. DOI: 10.1007/s10350-004-0651-7. View

16.

Maslekar S, Smith K, Harji D, Griffiths B, Sagar P . Injectable collagen for the treatment of fecal incontinence: long-term results. Dis Colon Rectum. 2013; 56(3):354-9. DOI: 10.1097/DCR.0b013e3182805276. View

17.

Hull T, Giese C, Wexner S, Mellgren A, Devroede G, Madoff R . Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence. Dis Colon Rectum. 2013; 56(2):234-45. DOI: 10.1097/DCR.0b013e318276b24c. View

18.

Zbar A, Aslam M, Gold D, Gatzen C, Gosling A, Kmiot W . Parameters of the rectoanal inhibitory reflex in patients with idiopathic fecal incontinence and chronic constipation. Dis Colon Rectum. 1998; 41(2):200-8. DOI: 10.1007/BF02238249. View

19.

Raghavan S, Gilmont R, Miyasaka E, Somara S, Srinivasan S, Teitelbaum D . Successful implantation of bioengineered, intrinsically innervated, human internal anal sphincter. Gastroenterology. 2011; 141(1):310-9. PMC: 3129458. DOI: 10.1053/j.gastro.2011.03.056. View

20.

Wang X, DaSilva G, Maron D, Cracco A, Wexner S . Outcomes of Reimplantation of the Artificial Bowel Sphincter. Dis Colon Rectum. 2016; 59(2):122-6. DOI: 10.1097/DCR.0000000000000521. View