RRC ID 34733
Author Sato Y, Kobayashi H, Higuchi T, Shimada Y, Era T, Kimura S, Eto Y, Ida H, Ohashi T.
Title Disease modeling and lentiviral gene transfer in patient-specific induced pluripotent stem cells from late-onset Pompe disease patient.
Journal Mol Ther Methods Clin Dev
Abstract Pompe disease is an autosomal recessive inherited metabolic disease caused by deficiency of acid α-glucosidase (GAA). Glycogen accumulation is seen in the affected organ such as skeletal muscle, heart, and liver. Hypertrophic cardiomyopathy is frequently seen in the infantile onset Pompe disease. On the other hand, cardiovascular complication of the late-onset Pompe disease is considered as less frequent and severe than that of infantile onset. There are few investigations which show cardiovascular complication of late onset Pompe disease due to the shortage of appropriate disease model. We have generated late-onset Pompe disease-specific induced pluripotent stem cell (iPSC) and differentiated them into cardiomyocytes. Differentiated cardiomyocyte shows glycogen accumulation and lysosomal enlargement. Lentiviral GAA rescue improves GAA enzyme activity and glycogen accumulation in iPSC. The efficacy of gene therapy is maintained following the cardiomyocyte differentiation. Lentiviral GAA transfer ameliorates the disease-specific change in cardiomyocyote. It is suggested that Pompe disease iPSC-derived cardiomyocyte is replicating disease-specific changes in the context of disease modeling, drug screening, and cell therapy.
Volume 2
Pages 15023
Published 2015
DOI 10.1038/mtm.2015.23
PII S2329-0501(16)30035-3
PMID 26199952
PMC PMC4495721
IF 3.681
Times Cited 11
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL
Resource
DNA material CSII-EF-MCS (RDB04378)