Kawagoe S 1 , Higuchi T 1 , Meng X 2 , shimada Y 1 , Shimizu H 1 , Fukuda T 1 , Nakahata T 3 , Fukada S 4 , Ida H 1 , Kobayashi H 1 , Ohashi T 1 , Eto Y . 1 1 Jikei University School of Medicine, Tokyo, Japan 2 Baylor Research Institute, Dallas, United States 3 Kyoto University, Kyoto, Japan 4 Osaka University, Osaka, Japan Background: Pompe disease (GSD-II) accumulates glycogen due to a deficiency of acid-α-glucosidase(GAA).Induced pluripotent stem (iPS) cell technology facilitates the study of the pathogenesis of Pompe disease and might eventually enable the development of autologous cell transplantation therapy. Objectives: We generated iPS cells from somatic cells by introducing reprogramming factors (Oct3/4, Sox2, Klf4 and c-Myc). Pompe-iPS cells were differentiated into skeletal muscle(SM) cells in Matrigel.-coated plates. Results: Our study first demonstrates the ability to generate iPS cells from a mouse model of Pompe disease. Initially, mouse fibroblasts were harvested from GAA knockout mice, and three reprogramming factors (Oct3/4, Sox2 and Klf4) were transfected into the isolated donor cells using a retroviral vector. These iPS cells also showed decreased levels of GAA enzymatic activity and strong staining with PAS and ACP. Spindle-shaped SM cells were successfully generated from Pompe-iPS cells and showed spontaneous contraction and positive staining with the MHC antibody. EM picture of SM cells showed typical morphological features. Furthermore, Pompe SM cells accumulated massive glycogen in lysosomes.