Tissue Regeneration of the Vocal Fold Using Bone Marrow Mesenchymal Stem Cells and Synthetic Extracellular Matrix Injections in Rats

Objective—To determine the effectiveness of bone marrow mesenchymal stem cell (BM-MSC) transplantation in isolation or within a synthetic extracellular matrix (sECM) for tissue regeneration of the scarred vocal fold lamina propria. Methods—In vitro stability and compatibility of mouse BM-MSC embedded in sECM was assessed by flow cytometry detection of BM-MSC marker expression and proliferation. Eighteen rats were subjected to vocal fold injury bilaterally, followed by one month post-treatment with unilateral injections of saline or sECM hydrogel (Extracel), GFP-mouse BM-MSC or BM-MSC suspended in sECM. Outcomes measured one month after treatment included procollagen-III, fibronectin, hyaluronan synthase-III (HAS3), hyaluronidase (HYAL3), smooth muscle actin (SMA) and transforming growth factor-beta 1(TGF-β1) mRNA expression. The persistence of GFP BM-MSC, proliferation, apoptosis and myofibroblast differentiation was assessed by immunofluorescence. Results—BM-MSC grown in vitro within sECM express Sca-1, are positive for hyaluronan receptor CD44 and continue to proliferate. In the in vivo study, groups injected with BM-MSC ha