Abstract 19051: Characterization of Induced Pluripotent Stem Cell-Derived Cardiomyocytes Using Human Adult Cardiac Progenitor Cells or Patient-Matched Fibroblasts
Introduction: Induced pluripotent stem cells (iPSCs) are a unique source of cardiomyocytes (CMs) for disease modelling and regenerative medicine. Multiple cell types have been reprogrammed to iPSCs. The tissue of origin of the reprogrammed cells may affect iPSC characteristics after establishing their pluripotent state.
Hypothesis: Here we compare reprogramming of adult human cardiac-resident progenitor cells (CPCs) and skin fibroblasts (Fib) into iPSCs, and the respective iPSC-derived CMs.
Methods and Results: CPCs and skin fibroblasts from the same donors were reprogrammed into iPSCs using OCT4, SOX2, KLF4 and MYC. PSC induction was documented by embryonic stem cell (ESC)-like colonies, pluripotency markers expression, and generation of cell derivatives from all three germ layers. CPC-derived iPSC-CMs (CPC-iPSC-CMs) showed higher expression levels of cardiac-specific sarcomeric proteins compared to Fib-iPSC-CMs. Extracellular field potentials (FPs) from spontaneously beating areas of iPSC-CMs were recorded by multi-electrode arrays (MEA). Both CPC- and Fib-iPSC-CMs revealed Na+ and late L-type Ca2+ currents (INa and ICaL, respectively) and functional rapid component of the delayed rectifier K+ current (IKr), as assessed using the IKr channel blocker E4031. IKs channel blocker JNJ303 and epinephrine affected the slow component of the delayed rectifier K+ current (IKs) only in CPC-iPSC-CMs, thus suggesting the presence of functional channel.
Conclusions: Adult human CPCs can be reprogrammed to iPSCs, from which CMs can be derived. CPC-iPSC-CMs express higher levels of sarcomeric proteins and display more mature electrophysiological features, such as functional IKs, compared to Fib-iPSC-CMs.
Author Disclosures: C. Altomare: None. E. Pianezzi: None. E. Cervio: None. V. Biemmi: None. A. Ciullo: None. S. Bolis: None. P. Benzoni: None. G. Camici: None. T. Moccetti: None. L. Barile: None. G. Vassalli: None.
- © 2016 by American Heart Association, Inc.