Faculty Collaboration Database

Dystrophin-deficient cardiomyocytes derived from human urine: new biologic reagents for drug discovery. Stem Cell Res 2014 Mar;12(2):467-80

Date

01/18/2014

Pubmed ID

24434629

Pubmed Central ID

PMC3966181

DOI

10.1016/j.scr.2013.12.004

Scopus ID

2-s2.0-84892470978 (requires institutional sign-in at Scopus site)   102 Citations

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.

Author List

Guan X, Mack DL, Moreno CM, Strande JL, Mathieu J, Shi Y, Markert CD, Wang Z, Liu G, Lawlor MW, Moorefield EC, Jones TN, Fugate JA, Furth ME, Murry CE, Ruohola-Baker H, Zhang Y, Santana LF, Childers MK

Author

Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Animals
Case-Control Studies
Cell Differentiation
Cells, Cultured
Drug Discovery
Dystrophin
Female
Humans
Induced Pluripotent Stem Cells
Kruppel-Like Transcription Factors
Male
Mice
Mice, Inbred NOD
Mice, SCID
Muscular Dystrophy, Duchenne
Myocytes, Cardiac
Proto-Oncogene Proteins c-myc
Telomerase
Young Adult