Singh J., and 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.00112.2012 Details
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.
Protein analysis on intact and reconstructed IAS tissue revealed no significant differences in the expression of major signal transduction proteins, such as RhoA/ROCK, PKCα, CPI-17, and p-CPI17. Immunocytochemical analysis revealed high levels of smooth muscle α-actin. Hence, reconstructs were not only functional but also phenotypically similar to intact IAS tissue.
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.