1. Dystrophin-deficient cardiomyocytes derived from human urine: New biologic reagents for drug discovery
- Author
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Guan, Xuan, Mack, David L, Moreno, Claudia M, Strande, Jennifer L, Mathieu, Julie, Shi, Yingai, Markert, Chad D, Wang, Zejing, Liu, Guihua, Lawlor, Michael W, Moorefield, Emily C, Jones, Tara N, Fugate, James A, Furth, Mark E, Murry, Charles E, Ruohola-Baker, Hannele, Zhang, Yuanyuan, Santana, Luis F, and Childers, Martin K
- Subjects
Medical Biotechnology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Duchenne/ Becker Muscular Dystrophy ,Stem Cell Research ,Pediatric ,Stem Cell Research - Induced Pluripotent Stem Cell ,Regenerative Medicine ,Cardiovascular ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Genetics ,Rare Diseases ,Muscular Dystrophy ,2.1 Biological and endogenous factors ,5.2 Cellular and gene therapies ,Adult ,Animals ,Case-Control Studies ,Cell Differentiation ,Cells ,Cultured ,Drug Discovery ,Dystrophin ,Female ,Humans ,Induced Pluripotent Stem Cells ,Kruppel-Like Factor 4 ,Kruppel-Like Transcription Factors ,Male ,Mice ,Mice ,Inbred NOD ,Mice ,SCID ,Muscular Dystrophy ,Duchenne ,Myocytes ,Cardiac ,Proto-Oncogene Proteins c-myc ,Telomerase ,Young Adult ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology ,Medical biotechnology ,Oncology and carcinogenesis - Abstract
The ability to extract somatic cells from a patient and reprogram them to pluripotency opens up new possibilities for personalized medicine. Induced pluripotent stem cells (iPSCs) have been employed to generate beating cardiomyocytes from a patient's skin or blood cells. Here, iPSC methods were used to generate cardiomyocytes starting from the urine of a patient with Duchenne muscular dystrophy (DMD). Urine was chosen as a starting material because it contains adult stem cells called urine-derived stem cells (USCs). USCs express the canonical reprogramming factors c-myc and klf4, and possess high telomerase activity. Pluripotency of urine-derived iPSC clones was confirmed by immunocytochemistry, RT-PCR and teratoma formation. Urine-derived iPSC clones generated from healthy volunteers and a DMD patient were differentiated into beating cardiomyocytes using a series of small molecules in monolayer culture. Results indicate that cardiomyocytes retain the DMD patient's dystrophin mutation. Physiological assays suggest that dystrophin-deficient cardiomyocytes possess phenotypic differences from normal cardiomyocytes. These results demonstrate the feasibility of generating cardiomyocytes from a urine sample and that urine-derived cardiomyocytes retain characteristic features that might be further exploited for mechanistic studies and drug discovery.
- Published
- 2014