Our goal is understanding mechanisms of muscle specificity involved in of various types of muscular dystrophy in order to enable targeted therapies that effectively treat the affected muscle. Craniofacial muscles differ from limb/trunk muscles in their distinctive embryonic origins, muscle stem cell activity and muscle fiber types. In addition, craniofacial muscles show differential susceptibility to each type of muscular dystrophy. For instance, while oculopharyngeal muscular dystrophy (OPMD) mainly affects the eye and pharyngeal muscles, they are not affected in Duchenne muscular dystrophy (DMD). Therefore, craniofacial muscle research is necessary for developing targeted therapies for affected muscles in each muscular dystrophy. To achieve this goal, we use proteomic and transcriptomic approach to compare craniofacial and limb muscles of DMD (as a limb myopathy dominant MD) or OPMD (as a craniofacial myopathy dominant MD) model mice. We generate in vitro muscle models using muscle stem cells, called satellite cells, to explore the mechanism of muscle specificity in each MD.
Other goals include developing transplantable muscle patches to treat congenital (cleft lip and palate) and acquired (pharyngocutaneous fistula after total laryngectomy or trauma) craniofacial deformality/volumetric muscle loss (VML). Current surgical treatments require a muscle flap from a distal muscle, which often causes additional complications including muscle volume loss and infections. One possible solution is to use a craniofacial muscle patch that is created using a patient’s own induced pluripotent stem cell (iPSC) as alternative tissue resources. iPSC-derived cellular resources for tissue engineering provide unlimited cell numbers for fabrication and minimum immunological control for transplantation. To achieve this goal, we have developed a protocol to differentiate craniofacial muscle cells from human iPSC and to culture them