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In vitro evaluation of anti‐fibrotic effects of select cytokines for vocal fold scar treatment
Author(s) -
Chen Hongyu,
ErndtMarino Josh,
DiazRodriguez Patricia,
Kulwatno Jonathan,
JimenezVergara Andrea C.,
Thibeault Susan L,
Hahn Mariah S.
Publication year - 2019
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.34198
Subject(s) - hepatocyte growth factor , proinflammatory cytokine , extracellular matrix , fibrosis , pathology , fibroblast , cytokine , in vitro , interleukin , inflammation , immunology , chemistry , medicine , cancer research , microbiology and biotechnology , biology , biochemistry , receptor
Scarring of the vocal fold lamina propria (LP) can cause considerable voice disorders due to reduced pliability in scar tissue, attributed in part to abnormal extracellular matrix (ECM) deposition produced by the fibrotic vocal fold fibroblast (fVFF). Cytokines with anti‐fibrotic potential have been investigated to limit abnormal LP ECM, but are limited by the need for repeat injections. Moreover, the potentially significant role played by activated macrophages (AMOs) is usually not considered even though the interaction between AMO and fibrotic fibroblasts is known to regulate scar formation across different tissues. AMO are also regulated by cytokines that are used for LP scar removal, but little is known about AMO behaviors in response to these cytokines within the context of LP scar. In the present study, we evaluated anti‐fibrotic effects of hepatocyte growth factor (HGF), interleukin‐10 (IL‐10) and interleukin‐6 (IL‐6) in a 3D, in vitro fVFF‐AMO co‐culture system using poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Data from all cytokines was synthesized into a heat‐map that enabled assessment of specific associations between AMO and fVFF phenotypes. Cumulatively, our results indicated that both HGF and IL‐10 are potentially anti‐fibrotic (reduction in fibrotic markers and enhancement in normal, anti‐fibrotic VFF markers), while IL‐6 displays more complex, marker specific effects. Possible associations between AMO and fVFF phenotypes were found and may highlight a potential desirable macrophage phenotype. These data support the therapeutic potential of HGF and IL‐10 for LP scar treatment, and shed light on future strategies aimed at targeting specific AMO phenotypes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1056–1067, 2019.