• Open Access

Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure

Authors

  • Mihaela Gherghiceanu,

    1. ‘Victor Babeş’ National Institute of Pathology, Bucharest, Romania
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    • Both the authors contributed equally to this work.

  • Lili Barad,

    1. The Sohnis Family Stem Cells Center, Haifa, Israel
    2. The Rappaport Institute, Haifa, Israel
    3. Rappaport Faculty of Medicine, Technion, Haifa, Israel
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    • Both the authors contributed equally to this work.

  • Atara Novak,

    1. The Sohnis Family Stem Cells Center, Haifa, Israel
    2. The Rappaport Institute, Haifa, Israel
    3. Rappaport Faculty of Medicine, Technion, Haifa, Israel
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  • Irina Reiter,

    1. The Sohnis Family Stem Cells Center, Haifa, Israel
    2. The Rappaport Institute, Haifa, Israel
    3. Rappaport Faculty of Medicine, Technion, Haifa, Israel
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  • Joseph Itskovitz-Eldor,

    1. The Sohnis Family Stem Cells Center, Haifa, Israel
    2. Rappaport Faculty of Medicine, Technion, Haifa, Israel
    3. Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel
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  • Ofer Binah,

    Corresponding author
    1. The Sohnis Family Stem Cells Center, Haifa, Israel
    2. The Rappaport Institute, Haifa, Israel
    3. Rappaport Faculty of Medicine, Technion, Haifa, Israel
      Ofer BINAH, Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, P.O. Box 9649, Haifa 31096, Israel. Tel.: +972-48295262 Fax: +972-48513919 E-mail: binah@tx.technion.ac.il  L.M. POPESCU, Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, P.O. Box 35-29, Bucharest 35, Romania. Tel.: +40-744-535298 Fax: +40-21-3124885 E-mail: lpopescu@jcmm.org
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  • L.M. Popescu

    Corresponding author
    1. ‘Victor Babeş’ National Institute of Pathology, Bucharest, Romania
    2. Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania
      Ofer BINAH, Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, P.O. Box 9649, Haifa 31096, Israel. Tel.: +972-48295262 Fax: +972-48513919 E-mail: binah@tx.technion.ac.il  L.M. POPESCU, Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, P.O. Box 35-29, Bucharest 35, Romania. Tel.: +40-744-535298 Fax: +40-21-3124885 E-mail: lpopescu@jcmm.org
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Ofer BINAH, Department of Physiology, Ruth & Bruce Rappaport Faculty of Medicine, P.O. Box 9649, Haifa 31096, Israel. Tel.: +972-48295262 Fax: +972-48513919 E-mail: binah@tx.technion.ac.il  L.M. POPESCU, Department of Cellular and Molecular Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, P.O. Box 35-29, Bucharest 35, Romania. Tel.: +40-744-535298 Fax: +40-21-3124885 E-mail: lpopescu@jcmm.org

Abstract

Induced pluripotent stem cells (iPSC) are generated from fully differentiated somatic cells that were reprogrammed into a pluripotent state. Human iPSC which can be obtained from various types of somatic cells such as fibroblasts or keratinocytes can differentiate into cardiomyocytes (iPSC-CM), which exhibit cardiac-like transmembrane action potentials, intracellular Ca2+ transients and contractions. While major features of the excitation-contraction coupling of iPSC-CM have been well-described, very little is known on the ultrastructure of these cardiomyocytes. The ultrastructural features of 31-day-old (post-plating) iPSC-CM generated from human hair follicle keratinocytes (HFKT-iPSC-CM) were analysed by electron microscopy, and compared with those of human embryonic stem-cell-derived cardiomyocytes (hESC-CM). The comparison showed that cardiomyocytes from the two sources share similar proprieties. Specifically, HFKT-iPSC-CM and hESC-CM, displayed ultrastructural features of early and immature phenotype: myofibrils with sarcomeric pattern, large glycogen deposits, lipid droplets, long and slender mitochondria, free ribosomes, rough endoplasmic reticulum, sarcoplasmic reticulum and caveolae. Noteworthy, the SR is less developed in HFKT-iPSC-CM. We also found in both cell types: (1) ‘Ca2+-release units’, which connect the peripheral sarcoplasmic reticulum with plasmalemma; and (2) intercellular junctions, which mimic intercalated disks (desmosomes and fascia adherens). In conclusion, iPSC and hESC differentiate into cardiomyocytes of comparable ultrastructure, thus supporting the notion that iPSC offer a viable option for an autologous cell source for cardiac regenerative therapy.

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