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Dystrophin-deficient cardiomyocytes derived from human urine: new biologic reagents for drug discovery.
- Source :
-
Stem cell research [Stem Cell Res] 2014 Mar; Vol. 12 (2), pp. 467-80. Date of Electronic Publication: 2013 Dec 23. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2013. Published by Elsevier B.V.)
- Subjects :
- Adult
Animals
Case-Control Studies
Cell Differentiation physiology
Cells, Cultured
Drug Discovery
Female
Humans
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors biosynthesis
Kruppel-Like Transcription Factors urine
Male
Mice
Mice, Inbred NOD
Mice, SCID
Myocytes, Cardiac cytology
Proto-Oncogene Proteins c-myc biosynthesis
Proto-Oncogene Proteins c-myc urine
Telomerase urine
Young Adult
Dystrophin deficiency
Induced Pluripotent Stem Cells pathology
Muscular Dystrophy, Duchenne pathology
Muscular Dystrophy, Duchenne urine
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1876-7753
- Volume :
- 12
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Stem cell research
- Publication Type :
- Academic Journal
- Accession number :
- 24434629
- Full Text :
- https://doi.org/10.1016/j.scr.2013.12.004