Towards a better anus – how bioengineering can help incontinence

Singh J.和Rattan S.（2012）. Bioengineered human internal anal sphincter (IAS) reconstructs with functional and molecular properties similar to intact IAS. American Journal of Physiology - Gastrointestinal and Liver Physiology,DOI: 10.1152/ajpgi.00112.2012Details

Fecal incontinence (FI) is an age-related disorder involving the inability to prevent accidental bowel movements. Its prevalence in US populations is about 1 in every 12 adults between 20 and >70 years of age. For sufferers this can lead to considerable distress, particularly in social situations.

The basal tone in the internal anal sphincter (IAS) muscle normally prevents unwanted bowel movements. Failure to maintain this tone leads to FI. Current treatment options include dieting, pelvic floor exercises, sphincteroplasty (surgical repair of the internal sphincter) and chronic electrical stimulation – none of which are entirely satisfactory.

A promising option that may someday be viable clinically uses a tissue engineering approach. As Singh and Rattan (2012) demonstrate in their recent study “the development of bioengineered IAS reconstructs has significant implications in the replacement of the dysfunctional IAS”.

By culturing smooth muscle cells (SMCs) from isolated IAS human explants and seeding them over custom designed silicone moulds, Singh and Rattan showed that within 72 hours SMCs can be transformed into IAS reconstructs. Furthermore, the reconstructs were shown to be functional.

Using isometric force transducers and a PowerLab, reconstructs developed basal tone of 0.68 ± 0.26 mN, which was regulated primarily via the RhoA/ROCK pathway, shown using a ROCK inhibitor (Y27632). Basal tone increased in response to contractile agents (bethanechol and KCl) and decreased in response to relaxing agents, isoproterenol and Y27632.

对完整和重建的IAS组织的蛋白质分析显示，主要信号转导蛋白的表达没有显着差异，例如RhoA/Rock，PKCα，CPI-17和P-CPI17。免疫细胞化学分析显示，平滑肌α-肌动蛋白的高水平。因此，重建不仅功能性，而且在表型上与完整的IAS组织相似。

Speculatively, once transplanted the reconstructs will integrate in the region of interest; however only clinical studies will show the long-term viability of this new approach.