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Letter to the Editor| Volume 157, ISSUE 1, P177-178, January 2015

Appropriately sized bioengineered human external anal sphincter constructs

      We read with interest the article entitled “Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells” by Raghavan et al.
      • Raghavan S.
      • Miyasaka E.A.
      • Gilmont R.R.
      • Somara S.
      • Teitelbaum D.H.
      • Bitar K.N.
      Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells.
      The authors demonstrated that the implanted bioengineered constructs became infiltrated by host microvasculature and when explanted after 4 weeks exhibited spontaneous active tone and neuronally mediated relaxation. We support the views of the authors that bioengineered constructs used in an additive manner hold promise for restoring continence in patients with damaged or degenerated anal sphincter muscle. As the authors point out, however, for this approach to be of clinical value, there remains a need for in situ evaluation of contraction, neuronal responsiveness, and vascularization that resemble more closely future use in humans. This represents an Achilles' heel for clinical translation for the majority of tissue-engineered constructs reported at a preclinical stage. One of the major challenges for future clinical translation of bioengineered constructs is recapitulation of the size of human organs.
      • Rustad K.C.
      • Sorkin M.
      • Levi B.
      • Longaker M.T.
      • Gurtner G.C.
      Strategies for organ level tissue engineering.
      Magnetic resonance imaging indicates the inner diameter of the internal anal sphincter (IAS) in humans is in the region of 7–9 mm at rest but increases to 30 mm in diameter when distended.
      • Huebner M.
      • Margulies R.U.
      • Fenner D.E.
      • Ashton-Miller J.A.
      • Bitar K.N.
      • DeLancey J.O.
      Age effects on internal anal sphincter thickness and diameter in nulliparous females.
      • Duthie H.L.
      Progress report. Anal continence.
      The IAS constructs reported by the authors' group to date are relatively small, with a luminal diameter measuring 5 mm which,
      • Hecker L.
      • Baar K.
      • Dennis R.G.
      • Bitar K.N.
      Development of a three-dimensional physiological model of the internal anal sphincter bioengineered in vitro from isolated smooth muscle cells.
      • Raghavan S.
      • Lam M.T.
      • Foster L.L.
      • Gilmont R.R.
      • Somara S.
      • Takayama S.
      • et al.
      Bioengineered three-dimensional physiological model of colonic longitudinal smooth muscle in vitro.
      although adequate for orthotopic implantation in small rodents, are not suitable for translation to humans.
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      References

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        • Miyasaka E.A.
        • Gilmont R.R.
        • Somara S.
        • Teitelbaum D.H.
        • Bitar K.N.
        Perianal implantation of bioengineered human internal anal sphincter constructs intrinsically innervated with human neural progenitor cells.
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