Objectives: Scarring caused by trauma, postcancer treatment, or inflammation in the vocal folds is associated with stiffness of the lamina propria and results in severe voice problems. Currently there is no effective treatment. Human embryonic stem cells (hESC) have been recognized as providing a potential resource for cell transplantations, but in the undifferentiated state, they are generally not considered for therapeutic use due to risk of inadvertent development. This study assesses the functional potential of hESC to prevent or diminish scarring and improve viscoelasticity following grafting into scarred rabbit vocal folds.
Study design: hESC were injected into 22 scarred vocal folds of New Zealand rabbits. After 1 month, the vocal folds were dissected and analyzed for persistence of hESC by fluorescence in situ hybridization using a human specific probe, and for differentiation by evaluation in hematoxylin-eosin-stained tissues. Parallel-plate rheometry was used to evaluate the functional effects, i.e., viscoelastic properties, after treatment with hESC.
Results: The results revealed significantly improved viscoelasticity in the hESC-treated vs. non-treated vocal folds. An average of 5.1% engraftment of human cells was found 1 month after hESC injection. In the hESC-injected folds, development compatible with cartilage, muscle and epithelia in close proximity or inter-mixed with the appropriate native rabbit tissue was detected in combination with less scarring and improved viscoelasticity.
Conclusions: The histology and location of the surviving hESC-derived cells strongly indicate that the functional improvement was caused by the injected cells, which were regenerating scarred tissue. The findings point toward a strong impact from the host microenvironment, resulting in a regional specific in vivo hESC differentiation and regeneration of three types of tissue in scarred vocal folds of adult rabbits.