Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment

R. S. Bartlett, J. T. Guille, X. Chen, M. B. Christensen, S. F. Wang, S. L. Thibeault

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. Methods Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (RT-PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. Results and discussion Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]β1, alpha smooth muscle actin, interleukin-1β, interleukin-17β and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC–treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair.

Original languageEnglish (US)
Pages (from-to)1284-1296
Number of pages13
JournalCytotherapy
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Keywords

  • elasticity
  • fibrosis
  • hyaluronic acid
  • hydrogel
  • mesenchymal stromal cells
  • rheology
  • viscosity
  • vocal cord

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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