Development of 3-dimensional human skeletal muscle tissue models of Limb-Girdle Muscular Dystrophy 2B
We have recently made progress in using 3D cell culture techniques to engineer functional skeletal muscle tissues from human pluripotent stem cells. We will further optimize this technology and apply it to generate contractile muscle tissues using induced pluripotent stem cells (iPSCs) from three LGMD2B patients and two healthy human donors. The resulting iPSC-derived dysferlin-deficient human muscle tissues will be systematically characterized by various structural, functional, and molecular assays. Regenerative responses to muscle injury in vitro will be studied to establish the similarity to known pathological responses in vivo. Eventually, we expect that establishing this human LGMD2B muscle model will aid fundamental studies of dysferlinopathies and enable pre-clinical testing of candidate drugs in a personalized fashion.