Macrophage Response to Allogeneic Adipose Tissue-Derived Stromal Cells in Hyaluronan-Based Hydrogel in a Porcine Vocal Fold Injury Model
- Authors
- King, Suzanne N.; Woo, Joo Hyun; Tang, Sharon; Thibeault, Susan L.
- Issue Date
- Jun-2017
- Publisher
- SAGE PUBLICATIONS INC
- Keywords
- vocal fold; adipose; mesenchymal stem/stromal cells; hyaluronic acid; macrophages; surgical injury; inflammation; wound healing; injury
- Citation
- ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, v.126, no.6, pp.463 - 477
- Journal Title
- ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
- Volume
- 126
- Number
- 6
- Start Page
- 463
- End Page
- 477
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6033
- DOI
- 10.1177/0003489417702923
- ISSN
- 0003-4894
- 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. Method: 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-alpha, TGF beta, IL-10, IL-4, IFN gamma, IL-12, FGF2, CollAl, 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.
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