Application of differentiated human tonsil–derived stem cells to trembler-J mice

Introduction: Mesenchymal stem cells (MSCs) can differentiate into various cell types. Methods: In this study we investigated the potential of human tonsil–derived MSCs (T-MSCs) for neuromuscular regeneration in trembler-J (Tr-J) mice, a model for Charcot–Marie–Tooth disease type 1A (CMT1A). Results: T-MSCs differentiated toward skeletal myocytes with increased expression of skeletal muscle–related markers (including troponin I type 1, and myogenin), and the formation of myotubes in vitro. In-situ transplantation of T-MSC–derived myocytes (T-MSC myocytes) into the gastrocnemius muscle in Tr-J mice enhanced motor function, with recovery of compound muscle action potential amplitudes. Morphology of the sciatic nerve and skeletal muscle recovered without the formation of teratomas, and the expression levels of nerve growth factor and glial-cell-line–derived neurotrophic factor were increased significantly in T-MSC myocytes compared with T-MSCs in vitro. Discussion: Transplantation of T-MSC myocytes could enable neuromuscular regeneration in patients with CMT1A. Muscle Nerve 57: 478–486, 2018.