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Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay

Please always quote using this URN: urn:nbn:de:bvb:20-opus-163320
  • Background: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material andBackground: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material and Methods: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F-2-fluoro-2-deoxy-D-glucose (\(^{18}\)F-FDG) and \(^{125}\)I-β-methyl-iodophenyl-pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. Results: After cardiac differentiation of hiPSC, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. Conclusions: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.show moreshow less

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Metadaten
Author: Naoko Nose, Rudolf A. Werner, Yuichiro Ueda, Katharina Günther, Constantin Lapa, Mehrbod S. Javadi, Kazuhito Fukushima, Frank Edenhofer, Takahiro Higuchi
URN:urn:nbn:de:bvb:20-opus-163320
Document Type:Preprint
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin
Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Language:English
Parent Title (English):International Journal of Cardiology
ISSN:0167-5273
Year of Completion:2018
Source:Naoko Nose, Rudolf A. Werner, Yuichiro Ueda, Katharina Günther, Constantin Lapa, Mehrbod S. Javadi, Kazuhito Fukushima, Frank Edenhofer, Takahiro Higuchi , Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay. Ijca (2018), doi:10.1016/j.ijcard.2018.06.089. (Preprint)
DOI:https://doi.org/10.1016/j.ijcard.2018.06.089
Sonstige beteiligte Institutionen:Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA
Sonstige beteiligte Institutionen:Department of Biomedical Imaging, National Cerebral and Cardiovascular Research Center, Suita, Japan
Sonstige beteiligte Institutionen:Institut for Molecular Biology and CMBI, Department of Genomics, Stem Cell Biology and Regenerative Medicine, Leopold-Franzens-University Innsbruck, Innsbruck, Austria
Sonstige beteiligte Institutionen:Division of Medical Technology and Science, Department of Medical Physics and Engineering, Course of Health Science, Osaka University Graduate School of Medicine, Suita Japan
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Stammzelle
Tag:cardiomyocytes; fatty acid; hiPSC-CM; induced pluripotent stem cells; stem cell therapy; tracer
Release Date:2018/06/26
EU-Project number / Contract (GA) number:701983
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International