AIMS: Induced pluripotent stem cells (iPSCs) provide a unique opportunity for the generation of patient-specific cells for use in disease modelling, drug screening, and regenerative medicine. The aim of this study was to compare human-induced pluripotent stem cells (hiPSCs) derived from different somatic cell sources regarding their generation efficiency and cardiac differentiation potential, and functionalities of cardiomyocytes. METHODS AND RESULTS: We generated hiPSCs from hair keratinocytes, bone marrow mesenchymal stem cells (MSCs), and skin fibroblasts by using two different virus systems. We show that MSCs and fibroblasts are more easily reprogrammed than keratinocytes. This corresponds to higher methylation levels of minimal promoter regions of the OCT4 and NANOG genes in keratinocytes than in MSCs and fibroblasts. The success rate and reprogramming efficiency was significantly higher by using the STEMCCA system than the OSNL system. All analysed hiPSCs are pluripotent and show phenotypical characteristics similar to human embryonic stem cells. We studied the cardiac differentiation efficiency of generated hiPSC lines (n = 24) and found that MSC-derived hiPSCs exhibited a significantly higher efficiency to spontaneously differentiate into beating cardiomyocytes when compared with keratinocyte-, and fibroblast-derived hiPSCs. There was no significant difference in the functionalities of the cardiomyocytes derived from hiPSCs with different origins, showing the presence of pacemaker-, atrial-, ventricular- and Purkinje-like cardiomyocytes, and exhibiting rhythmic Ca2+ transients and Ca2+ sparks in hiPSC-derived cardiomyocytes. Furthermore, spontaneously and synchronously beating and force-developing engineered heart tissues were generated. CONCLUSIONS: Human-induced pluripotent stem cells can be reprogrammed from all three somatic cell types, but with different efficiency. All analysed iPSCs can differentiate into cardiomyocytes, and the functionalities of cardiomyocytes derived from different cell origins are similar. However, MSC-derived hiPSCs revealed a higher cardiac differentiation efficiency than keratinocyte- and fibroblast-derived hiPSCs.
AIMS: Induced pluripotent stem cells (iPSCs) provide a unique opportunity for the generation of patient-specific cells for use in disease modelling, drug screening, and regenerative medicine. The aim of this study was to compare human-induced pluripotent stem cells (hiPSCs) derived from different somatic cell sources regarding their generation efficiency and cardiac differentiation potential, and functionalities of cardiomyocytes. METHODS AND RESULTS: We generated hiPSCs from hair keratinocytes, bone marrow mesenchymal stem cells (MSCs), and skin fibroblasts by using two different virus systems. We show that MSCs and fibroblasts are more easily reprogrammed than keratinocytes. This corresponds to higher methylation levels of minimal promoter regions of the OCT4 and NANOG genes in keratinocytes than in MSCs and fibroblasts. The success rate and reprogramming efficiency was significantly higher by using the STEMCCA system than the OSNL system. All analysed hiPSCs are pluripotent and show phenotypical characteristics similar to human embryonic stem cells. We studied the cardiac differentiation efficiency of generated hiPSC lines (n = 24) and found that MSC-derived hiPSCs exhibited a significantly higher efficiency to spontaneously differentiate into beating cardiomyocytes when compared with keratinocyte-, and fibroblast-derived hiPSCs. There was no significant difference in the functionalities of the cardiomyocytes derived from hiPSCs with different origins, showing the presence of pacemaker-, atrial-, ventricular- and Purkinje-like cardiomyocytes, and exhibiting rhythmic Ca2+ transients and Ca2+ sparks in hiPSC-derived cardiomyocytes. Furthermore, spontaneously and synchronously beating and force-developing engineered heart tissues were generated. CONCLUSIONS:Human-induced pluripotent stem cells can be reprogrammed from all three somatic cell types, but with different efficiency. All analysed iPSCs can differentiate into cardiomyocytes, and the functionalities of cardiomyocytes derived from different cell origins are similar. However, MSC-derived hiPSCs revealed a higher cardiac differentiation efficiency than keratinocyte- and fibroblast-derived hiPSCs.
Authors: Oscar J Abilez; Evangeline Tzatzalos; Huaxiao Yang; Ming-Tao Zhao; Gwanghyun Jung; Alexander M Zöllner; Malte Tiburcy; Johannes Riegler; Elena Matsa; Praveen Shukla; Yan Zhuge; Tony Chour; Vincent C Chen; Paul W Burridge; Ioannis Karakikes; Ellen Kuhl; Daniel Bernstein; Larry A Couture; Joseph D Gold; Wolfram H Zimmermann; Joseph C Wu Journal: Stem Cells Date: 2017-11-13 Impact factor: 6.277
Authors: Nadejda V Mezentseva; Jinpu Yang; Keerat Kaur; Grazia Iaffaldano; Mathieu C Rémond; Carol A Eisenberg; Leonard M Eisenberg Journal: Stem Cells Dev Date: 2012-11-07 Impact factor: 3.272
Authors: Michael Didié; Peter Christalla; Michael Rubart; Vijayakumar Muppala; Stephan Döker; Bernhard Unsöld; Ali El-Armouche; Thomas Rau; Thomas Eschenhagen; Alexander P Schwoerer; Heimo Ehmke; Udo Schumacher; Sigrid Fuchs; Claudia Lange; Alexander Becker; Wen Tao; John A Scherschel; Mark H Soonpaa; Tao Yang; Qiong Lin; Martin Zenke; Dong-Wook Han; Hans R Schöler; Cornelia Rudolph; Doris Steinemann; Brigitte Schlegelberger; Steve Kattman; Alec Witty; Gordon Keller; Loren J Field; Wolfram-Hubertus Zimmermann Journal: J Clin Invest Date: 2013-02-22 Impact factor: 14.808
Authors: E Castillo-Gómez; B Oliveira; D Tapken; S Bertrand; C Klein-Schmidt; H Pan; P Zafeiriou; J Steiner; B Jurek; R Trippe; H Prüss; W-H Zimmermann; D Bertrand; H Ehrenreich; M Hollmann Journal: Mol Psychiatry Date: 2016-08-09 Impact factor: 15.992
Authors: Lyndsay L Leach; Roxanne H Croze; Qirui Hu; Vignesh P Nadar; Tracy N Clevenger; Britney O Pennington; David M Gamm; Dennis O Clegg Journal: J Ocul Pharmacol Ther Date: 2016-05-16 Impact factor: 2.671