[HTML][HTML] Dystrophin-deficient cardiomyocytes derived from human urine: new biologic reagents for drug discovery

X Guan, DL Mack, CM Moreno, JL Strande, J Mathieu… - Stem cell …, 2014 - Elsevier
X Guan, DL Mack, CM Moreno, JL Strande, J Mathieu, Y Shi, CD Markert, Z Wang, G Liu…
Stem cell research, 2014Elsevier
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 …
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.
Elsevier