Myod Overexpression In A Myoblast-populated Decellularized Matrix Promotes Enhanced Healing In Wounded Muscle Tissue In Vivo
Mimi Wu Young, Seok Hong, David Dolivo, Thomas Mustoe, Robert Galiano.
Northwestern University, Chicago, IL, USA.
BACKGROUND-Volumetric muscle loss, caused by severe trauma or combat injury, results in extensive fibrosis and loss of muscle function due to destruction of the biomechanical and biochemical muscular microenvironment. As such, strategies that recapitulate native guidance and differentiation cues found in mature muscle tissue and enable repopulation of the site of defect with mature, functional muscle cells are highly desirable. METHODS-We overexpressed myoD, an early transcription factor that drives myogenic commitment and differentiation, in L6 rat myoblasts and characterized their differentiation in vitro. We then implanted decellularized muscle-derived matrices repopulated with myoD-overexpressing myoblasts or GFP-overexpressing myoblasts in rat latissimus dorsi defect models and assessed integration by gross appearance and expression of MHC by immunohistochemistry and Western blot analyses.RESULTS-We determined that MyoD-overexpressing myoblasts differentiated effectively in vitro. Decellularized rat muscle tissue-derived matrix populated with myoblasts integrated well into the latissimus dorsi in vivo. Matrices repopulated with myoD-overexpressing myoblasts demonstrated greater expression of MHC and increased formation of mature myofibrils at the defect site when implanted in vivo compared to matrices repopulated with GFP-overexpressing myoblasts. CONCLUSIONS-These data suggest that myoblast-repopulated allogeneic matrices may be useful in aiding functional muscle recovery. Our ongoing studies seek to determine the degree of functional muscle recovery yielded by this approach and by similar approaches, to investigate alternative matrix sources for optimal myogenic recovery, and to explore alternative cell sources that create the best conditions to promote healing in wounded muscle tissue.
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