title: Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Bartlett
authors.affiliation: Department of ENT and Head and Neck Surgery, University Hospital of Pointe à Pitre, Guadeloupe, French West Indies.
authors.forename: J T
authors.initials: JT
authors.lastname: Guille
authors.affiliation: Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: National Center for Voice and Speech, University of Utah, Salt Lake City, Utah, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Christensen
authors.affiliation: Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA. Electronic address: thibeault@surgery.wisc.edu.
authors.forename: S L
authors.initials: SL
authors.lastname: Thibeault
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011817:Rabbits; D012038:Regeneration / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014827:Vocal Cords / Q000166:cytology / Q000502:physiology* / Q000601:surgery* / Q000637:transplantation; D014945:Wound Healing; D055815:Young Adult
chemical_list: D053773:Transforming Growth Factor beta1
keywords: elasticity; fibrosis; hyaluronic acid; hydrogel; mesenchymal stromal cells; rheology; viscosity; vocal cord