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

J Cell Mol Med. 2011 Nov;15(11):2539-51. doi: 10.1111/j.1582-4934.2011.01417.x.

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 Ca(2+) 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) 'Ca(2+)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Caveolae / ultrastructure
  • Cell Differentiation*
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / physiology
  • Endoplasmic Reticulum / ultrastructure
  • Excitation Contraction Coupling
  • Fibroblasts / cytology
  • Hair Follicle / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / physiology
  • Keratinocytes / cytology
  • Membrane Potentials
  • Microscopy, Electron
  • Mitochondria, Heart / ultrastructure
  • Myocardial Contraction
  • Myocytes, Cardiac / ultrastructure*
  • Sarcoplasmic Reticulum / ultrastructure

Substances

  • Calcium