Laryngology

Tissue regeneration of the vocal fold using bone marrow mesenchymal stem cells and synthetic extracellular matrix injections in rats†

  1. Beatriz Quinchia Johnson DDS, PhD,
  2. Ryan Fox,
  3. Xia Chen MD, PhD,
  4. Susan Thibeault PhD*

Article first published online: 3 FEB 2010

DOI: 10.1002/lary.20782

Issue

The Laryngoscope

The Laryngoscope

Volume 120, Issue 3, pages 537–545, March 2010

Additional Information

How to Cite

Quinchia Johnson, B., Fox, R., Chen, X. and Thibeault, S. (2010), Tissue regeneration of the vocal fold using bone marrow mesenchymal stem cells and synthetic extracellular matrix injections in rats. The Laryngoscope, 120: 537–545. doi: 10.1002/lary.20782

Author Information

  1. Division of Otolaryngology–Head and Neck, Department of Surgery, University of Wisconsin–Madison, School of Medicine and Public Health, Madison, Wisconsin, U.S.A.

*5107 WIMR, 1111 Highland Ave., University of Wisconsin, Madison, WI 53705

  1. †

    This work was supported by National Institutes of Health grant NIH-NIDCD RO1 DC004336.

Publication History

  1. Issue published online: 16 FEB 2010
  2. Article first published online: 3 FEB 2010
  3. Manuscript Accepted: 19 OCT 2009

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (1210K)

Keywords:

  • Mesenchymal stem cells;
  • tissue engineering;
  • hydrogel;
  • extracellular matrix;
  • myofibroblast differentiation

Abstract

Objectives/Hypothesis.

To determine the effectiveness of bone marrow mesenchymal stem cell (BM-MSC) transplantation in isolation or within a synthetic extracellular matrix (sECM) for tissue regeneration of the scarred vocal fold lamina propria.

Methods.

In vitro stability and compatibility of mouse BM-MSC embedded in sECM was assessed by flow cytometry detection of BM-MSC marker expression and proliferation. Eighteen rats were subjected to vocal fold injury bilaterally, followed by 1 month post-treatment with unilateral injections of saline or sECM hydrogel (Extracel; Glycosan BioSystems, Inc., Salt Lake City, UT), green fluorescence protein (GFP)-mouse BM-MSC, or BM-MSC suspended in sECM. Outcomes measured 1 month after treatment included procollagen-III, fibronectin, hyaluronan synthase-III (HAS3), hyaluronidase (HYAL3), smooth muscle actin (SMA), and transforming growth factor-beta 1(TGF-β1) mRNA expression. The persistence of GFP BM-MSC, proliferation, apoptosis, and myofibroblast differentiation was assessed by immunofluorescence.

Results.

BM-MSC grown in vitro within sECM express Sca-1, are positive for hyaluronan receptor CD44, and continue to proliferate. In the in vivo study, groups injected with BM-MSC had detectable GFP-labeled BM-MSC remaining and showed proliferation and low apoptotic or myofibroblast markers compared to the contralateral side. Embedded BM-MSC in the sECM group exhibited increased levels of procollagen III, fibronectin, and TGF-β1. BM-MSC within sECM downregulated the expression of SMA compared to BM-MSC alone and exhibited upregulation of HYAL3 and no change in HAS3 compared to saline.

Conclusions.

Treatment of vocal fold scarring with BM-MSC injected in a sECM displayed the most favorable outcomes in ECM production, hyaluronan metabolism, myofibroblast differentiation, and production of TGF-β1. Furthermore, the combined treatment had no detectable cytotoxicity and preserved local cell proliferation. Laryngoscope, 2010

View Full Article (HTML) Get PDF (1210K)