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

Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3-Month Follow-Up Study.
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DOI:
10.1002/sctm.16-0458
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发表时间:
2017-09
影响因子:
6
通讯作者:
Bitar KN
Bitar KN
中科院分区:
医学2区
文献类型:
--
作者:
Bohl JL;Zakhem E;Bitar KN

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大便失禁(FI)是粪便物质的不自主通过。目前的治疗方法成功的结果有限。本研究的目的是开发一种被动FI的大型动物模型,并在植入工程化自体肛门内括约肌(IAS)生物括约肌后,在该模型中使用肛门直肠测压法证明粪便排泄的持续恢复。本研究使用了20只雌性家兔。将动物分为三组:(a)未处理组:家兔通过半括约肌切除术进行IAS损伤,未进行处理。(b)治疗组:通过半括约肌切除术,然后植入自体生物括约肌,对家兔进行IAS损伤。(c)假手术组:通过半括约肌切除术对家兔进行IAS损伤,然后重新进入手术部位,然后立即闭合,未植入生物括约肌。在基线、括约肌切除术后1个月、植入后3个月和假手术后,使用肛门直肠测压法测量静息肛门压力和直肠肛门抑制反射(RAIR)。括约肌切除术后,所有家兔均出现基础张力降低和RAIR丢失,提示FI。兔子也失去了肛门卫生。在未治疗组中,基础张力和RAIR的降低持续超过3个月。治疗组8只供体兔成功植入自体生物括约肌。生物括约肌植入后3个月,基础张力和RAIR恢复,并且与未治疗组和假手术组的兔子相比显着更高。在组织学上,与未给药组相比,给药组恢复了平滑肌重建和连续性。本研究的结果为FI的治疗提供了有希望的结果。结果表明,开发和验证被动FI的大动物模型的可行性。这项研究还显示了工程生物括约肌恢复粪便蠕动的功效,如测压所示。干细胞转化医学2017;6:1795-1802
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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DOI: 10.1097/dcr.0b013e3182805276
发表时间: 2013-03-01
影响因子: 3.9
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