Novel murine xenograft model for the evaluation of stem cell therapy for profound dysphagia

Maggie Kuhn, Amanda B. Black, M. Tausif Siddiqui, Jan Nolta, Peter C Belafsky

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Objectives/Hypothesis: Dysphagia is common and costly. Treatments are limited and innovative therapies are required. The tongue is essential for safe, effective swallowing and is a natural target for regenerative therapy. Muscle-derived stem cells (MDSCs) hold potential to restore dynamic function, and their application in the damaged tongue is appealing. We examined the safety and efficacy of human MDSC implantation into a novel mouse tongue model. Study Design: Animal study. Methods: Adult immune-deficient mice were randomized to surgical (hemiglossectomy) and nonsurgical groups. Animals underwent lingual injection of human MDSCs or saline (control). Groups were followed for 12 weeks. The primary outcome was MDSC survival measured by an in vivo imaging system (IVIS). Secondary outcomes included animal survival and weight. Comparisons were made using a Mann-Whitney U test with an α of .05. Results: Human MDSCs survived to the endpoint demonstrating 132% ± 465% and 15% ± 11% bioluminescence by IVIS at 12 weeks in hemiglossectomy and nonsurgical groups, respectively. All but one animal (hemiglossectomy with saline injection) survived to the study endpoint. Mean weight increased from baseline in all groups, with the greatest change observed in hemiglossectomy mice with MDSC injection (baseline 24.5 g ± 3.9 g; delta 5.9 g ± 4.6 g), exceeding the weight gain seen in surgical control mice (baseline 24.9 g ± 4.2 g, delta 2.7 g ± 1.4 g) (P = .04). Conclusions: MDSCs exhibited over 100% survival at 3 months when injected into an immune-deficient hemiglossectomy mouse model. Tongue-injured animals injected with MDSCs exhibited superior weight gain after hemiglossectomy than control animals (P < .05). These data support further investigation into the use of autologous MDSCs as a potential treatment for dysphagia secondary to tongue weakness and fibrosis.

Original languageEnglish (US)
JournalLaryngoscope
DOIs
StateAccepted/In press - 2017

Keywords

  • Animal model
  • Deglutition
  • Hemiglossectomy
  • Muscle-derived stem cells
  • Oropharyngeal dysphagia
  • Regenerative medicine
  • Swallowing
  • Tongue

ASJC Scopus subject areas

  • Otorhinolaryngology

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