title: Macrophage Response to Allogeneic Adipose Tissue-Derived Stromal Cells in Hyaluronan-Based Hydrogel in a Porcine Vocal Fold Injury Model.
abstract: OBJECTIVE
  Adipose tissue-derived stromal cells (ASC) embedded in hyaluronan scaffold is a beneficial prophylactic treatment for vocal fold (VF) surgical scar. Here, we investigated the macrophage inflammatory response to allogeneic ASC-constructs and identified changes in lamina propria extracellular matrix.
  
  
  METHODS
  Pig ASC were characterized and transfected with GFP+ lentivirus. Thirty-three pigs underwent VF biopsies, and after 3 days, gel alone, gel+pASC, placebo, or pASC alone was injected into wound bed. Animals were sacrificed 3, 7, or 26 days post-injection. Flow cytometry; qPCR for NF-α, TGFβ, IL-10, IL-4, IFNγ, IL-12, FGF2, Col1A1, and HGF; and immunohistochemistry for collagen, elastin, HA, and fibronectin were performed to characterize macrophage phenotype, quantify cytokine transcription, analyze extracellular matrix remodeling, and track GFP+ cells.
  
  
  RESULTS
  No significant differences were found in SWC3+/SWC9+ phenotype or mRNA expression between cells+gel, gel, or placebo. The ASC alone exhibited significantly greater collagen, gel alone resulted in significantly less hyaluronan, and gel+pASC significantly more fibronectin (all P < .05). The pASC-GFP+ were detected 26 days post-injection.
  
  
  CONCLUSIONS
  The ASC-constructs were biocompatible; they did not influence the macrophage inflammatory response or provoke increases in collagen expression. Long-term engraftment was confirmed.
authors.affiliation: 1 Department of Otolaryngology-Head and Neck Surgery and Communicative Disorders, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Suzanne N
authors.initials: SN
authors.lastname: King
authors.affiliation: 2 Department of Otorhinolaryngology-Head and Neck Surgery, Gil Medical Center, Gachon University, Seongnam, South Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Woo
authors.affiliation: 3 Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Tang
authors.affiliation: 3 Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Thibeault
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002921:Cicatrix / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology*; D009092:Mucous Membrane / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D017154:Stromal Cells / Q000502:physiology*; D013552:Swine; D054457:Tissue Scaffolds; D014827:Vocal Cords / Q000473:pathology* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid
keywords: adipose; hyaluronic acid; inflammation; injury; macrophages; mesenchymal stem/stromal cells; surgical injury; vocal fold; wound healing