Age effects on extracellular matrix production of vocal fold scar fibroblasts in rats

Abstract

Vocal fold (VF) fibroblasts are the central subject of interest in fibrogenesis and wound healing after VF injury. Scar fibroblasts (SF) exhibit an aberrant production of several extracellular matrix (ECM) components which lead either to VF fibrosis or scarless wound healing. This study aimed to investigate the role of age at the time of injury on ECM production of SF. This is designed as an animal study. VF injury was established unilaterally in eight male Sprague-Dawley rats [3 months of age (n = 4), 11 months of age (n = 4)], while the other side was left intact. Three months after injury the larynges were excised and fibroblasts were extracted from VF [normal fibroblasts (NF)–scar fibroblasts (SF)] and cultured in vitro. After first passage, VF fibroblasts were plated in 24-well plates and levels of hyaluronic acid (HA) and collagen type I were determined enzymatically from supernatant after 24 and 72 h. Cultured SF from younger animals produced significantly higher levels of HA compared to NF fibroblasts from the same animals. HA concentrations of the older animals did not differ significantly between the NF and SF cultures, but the range in SF cultures was large. In contrast to previous studies, we found that even 3 months after VF injury cultured SF from young animals expressed higher levels of HA in comparison to SF from older animals. No difference in collagen levels were observed between the younger and older animals. Age of animals is an essential factor during VF healing and has to be considered for study design.

Establishing principles of macromolecular crowding for in vitro fibrosis research of the vocal fold lamina propria

“…Recent publications by our group showed that age is, among others, an important factor when dealing with VFF. The cultured scar VFF of younger animals produced significantly higher levels of HA, even 3 months after injury, compared to the unaffected contralateral side and to the cultured scar VFF of older animals . We observed the same phenomenon under external stimulation for which the cultured sVFF of younger animals responded stronger to HGF‐stimulation …”

Vocal fold myofibroblast profile of scarring

“…Vocal fold fibroblasts provide structural support to the lamina propria by producing growth factors and matrix fibers . In the presence of vocal fold scar, fibroblasts exhibit an unbalanced production of ECM components, leading to fibrosis . The ability of myofibroblasts to generate contractile forces is due to accumulation of cytoplasm and cellular fibronectin, resulting from ECM reorganization .…”

“…1,16,17 In the presence of vocal fold scar, fibroblasts exhibit an unbalanced production of ECM components, leading to fibrosis. 18 The ability of myofibroblasts to generate contractile forces is due to accumulation of cytoplasm and cellular fibronectin, resulting from ECM reorganization. 19 Myofibroblasts that express a-SMA are considered to be activated contractile fibroblasts and primarily responsible for excessive ECM contraction deposition with scar.…”

Development and validation of a novel phonomimetic bioreactor

“…Injury to the VF due to vocal overuse or surgical procedures modify the behaviour of VFF, which may result in numerous VF pathologies (e.g. polyps, Reinke’s edema, VF scars) [7]. The resulting deterioration of the voice (dysphonia) reduces quality of life, leads to social withdrawal and affects the ability to work (e.g.…”