Glycated Chitosan Derivatives Inhibit Myofibroblast Form And Function In an Anchored Collagen Matrix
Tu Doan, Derek Newsome, Gang Xu, Melville Vaughan.
University of Central Oklahoma, Edmond, OK, USA.
Fibrotic diseases like Dupuytren's contracture (DC) involve scar formation and excess production of extracellular matrix components. The differentiation of fibroblasts into myofibroblasts plays a main role in DC as it generates contraction in areas without wound openings, leads to the deposition of scar tissue, and eventually flexes one or more fingers. Additionally the disease has a high recurrence rate. Previously we showed that glycated chitosan (GC), a polysaccharide used as an immunoadjuvant, inhibited myofibroblast differentiation in a DC fibroblast culture; our goal was to expand those results to include other DC cell lines and determine whether single-walled carbon nanotube-conjugated GC (SWNT-GC) would be similarly effective. The GC-incorporated and vehicle control (water) stress-relaxed collagen matrices, in vitro 3D models, were used to show the compaction (defined as anchored matrix height reduction) of DC fibroblasts. Matrix height was measured daily for 12 days using optical coherence tomography. Fibroblasts were unable to compact in GC- and SWNT-GC-collagen matrices to the same extent as vehicle control lattices. To determine the amount of tension generated, matrices were mechanically released from the substratum on day 12. Proliferative myofibroblasts were identified by the presence of alpha smooth muscle actin via immunofluorescent staining. Compared to control conditions there were fewer myofibroblasts in GC and SWNT-GC treatment but without significant decrease in the number of nonproliferative fibroblasts. This suggests that GC and SWNT-GC may be a possible treatment for the recurrent problem of fibrotic diseases by inhibiting fibroblast migration and myofibroblast phenotypes.
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