Editors' ChoiceTissue Engineering

Regenerative Medicine Gets Vocal

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Science Translational Medicine  29 Jan 2014:
Vol. 6, Issue 221, pp. 221ec17
DOI: 10.1126/scitranslmed.3008471

Without a functional larynx, breathing, swallowing, and speaking would be tremendously difficult. Laryngectomy is a radical surgery performed in cases of laryngeal cancer, other head and neck cancers, severe trauma, and severe damage to the larynx from radiation treatment. Thus, there is an unmet need in this patient population to regenerate a missing larynx.

Kitamura and colleagues examined the potential of an acellular extracellular matrix (ECM) scaffold to regenerate the larynx in a canine model. The scaffold was taken from pig urinary bladder, decellularized, and assembled to form a sheet with a flap designed to fit the vocal fold ridge. Dogs are a good model for larynx regeneration because they too have a “voice,” in the form of a bark. A partial laryngectomy was performed in five beagle dogs, and immediately after, the acellular scaffold was fitted to the surgical defect and sutured. Functional data were obtained 6 months after intervention and were within normal range in three of the five animals studied. Complete glottic closure and near-normal vibration pattern with normal phonation threshold pressure were achieved; in other words, the three dogs could bark. There was, however, variability among animals, and two did not recover larynx function, at least within the 6-month time frame. Histological analysis revealed regeneration of cartilage, vocal fold mucosa, and muscle, as well as complete re-epithelialization. More importantly, the scaffold supported regeneration of the different tissues in their original positions separately—namely, the defect area was populated by cartilage, muscle, and epithelium that connected to other cartilage, muscle, and epithelial tissue types around the injury site. Kitamura et al. believe that the scaffold recruited different cell types from the vicinity of the injury to regenerate the dogs’ larynx tissue.

As the authors themselves point out, the results obtained are encouraging, but additional work is needed to improve function and reduce interanimal variability. Strategies directed to avoiding scar tissue formation in the regenerated vocal fold mucosa may allow further recovery of the vibratory function. Dogs have larynges similar to those of humans, so upon optimization in the canine model, this simple ECM-based approach could translate to patients who have lost their voice to larynx cancer or trauma.

M. Kitamura et al., Glottic regeneration with a tissue-engineering technique, using acellular extracellular matrix scaffold in a canine model. J. Tissue Eng. Regen. Med., published online 8 January 2014 (10.1002/term.1855). [Abstract]

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