title: Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering.
abstract: OBJECTIVE
  One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds.
  
  
  METHODS
  Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH).
  
  
  RESULTS
  Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only.
  
  
  CONCLUSIONS
  Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.
authors.affiliation: 1 Department of Otolaryngology, School of Medicine, Fukushima Medical University, Fukushima City, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Imaizumi
authors.affiliation: 2 School of Communication Sciences and Disorders, McGill University, Montreal, QC, Canada.
authors.forename: Nicole Y K
authors.initials: NY
authors.lastname: Li-Jessen
authors.affiliation: 1 Department of Otolaryngology, School of Medicine, Fukushima Medical University, Fukushima City, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sato
authors.affiliation: 3 Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Yang
authors.affiliation: 4 Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Thibeault
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D048091:Guided Tissue Regeneration / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014827:Vocal Cords / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology
chemical_list: D020100:Hydrogels; D004815:Epidermal Growth Factor; D006820:Hyaluronic Acid
keywords: hyaluronic acid (HA) hydrogel; induced pluripotent stem cells (iPS); regeneration of the vocal folds; tissue engineering; vocal fold injection