What type of in vivo tissue engineering construct best facilitates tissue regeneration after vocal fold scarring?
Background: Vocal fold scarring is the cause of most cases of voice deficiencies after vocal fold injury. Current surgical and pharmaceutical interventions are often unsatisfactory and result in inconsistent short- and long-term outcomes.
Study Design: Stability and compatibility of bone marrow-derived mesenchymal stem cells (BM-MSC) transplanted in isolation or within an embedded synthetic extracellular matrix (sECM) were assessed with flow cytometry and immunofluorescence in 18 rats with vocal fold injury. Rats were treated with unilateral injections of saline or sECM hydrogel, along with green fluorescence protein (GFP) mouse BM-MSC or BM-MSC suspended in sECM.
Setting: University of Wisconsin-Madison
Synopsis: Comparison of flow cytometric studies of cell surface markers before and after growing mouse BM-MSC in sECM for three days indicated a preservation of extracellular marker expression, viability and mitotic activity. Combined injection of BM-MSC and sECM produced the most favorable extracellular matrix gene expression profile and a synergistic effect in hyaluronan-metabolizing enzymes gene expression compared to individual treatment. Immunofluorescence revealed persistence of GFP expression, cell proliferation, low cytotoxicity and low myofibroblast differentiation of the combined therapy. Physical constraints imposed on the study inhibited the acquisition of data from longer and shorter time points.
Bottom Line: In rats with injured vocal folds, injections with BM-MSC are beneficial in the context of an sECM in promoting ECM deposition and growth factor production without increasing myofibroblast differentiation, thereby preserving the qualities and biological competence of the replaced tissue.
Citation: Quinchia Johnson B, Fox R, Chen X, et al. Tissue regeneration of the vocal fold using bone marrow mesenchymal stem cells and synthetic extracellular matrix injections in rats. Laryngoscope. 2010;120(3):538-546.