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Comparative Study Highlights Utility of iPSC-derived Cardiomyocytes

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Review of “Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes” from STEM CELLS by Stuart P. Atkinson

The replacement of lost cardiomyocytes (CMs) with cells differentiated from embryonic stem cell (ESCs) represents an exciting treatment option for myocardial infarction (MI) and other cardiomyopathies [1, 2]. The possibility of immune rejection of ESC-derived cells has prompted some researchers to investigate patient-specific induced pluripotent stem cells (iPSCs) as an alternative pluripotent cell type for CM differentiation.

However, reported differences in gene expression profiles between ESCs and iPSCs [3, 4] fold the potential to negatively influence the functionality of differentiated cell types, including CMs. For this reason, a recent STEM CELLS study from the laboratories of Joseph C. Wu and Sang-Ging Ong (Stanford University School of Medicine, California, USA) sought to directly compare the therapeutic efficacy of ESC- and iPSC-derived CMs following transplantation in ischemic rat hearts [5] with a particular focus on the role of exosomes [6].

Differentiation of both human ESCs and iPSCs towards a CM fate employing a defined combination of small molecule inhibitors provided an 85% pure population for comparisons of sarcomeric structures, cardiac gene expression profiled, and electrophysiological properties. Encouragingly, the study highlighted a high degree of similarity between ESC-CMs and iPSC-CMs, and following injection into the hearts of subacute MI model rats, both cell types engrafted well and mediated a comparable functional improvement in cardiac function.

ESC- and iPSC-CMs may promote functional recovery via the secretion of paracrine acting factors, and so the study next compared exosomal microRNAs and long non-coding RNAs from both CM types. In line with the previously noted similarities, ESC- and iPSC-CMs expressed similar levels of these RNA species, including some with known cardioprotective properties.

The functional similarity between CMs derived from ESCs and iPSCs discovered in this “comparatively” exciting study will hopefully propel patient-specific iPSC-CMs towards clinical application, and forego the problem of immune rejection associated with ESC-CMs. Furthermore, the similarities in the expression patterns of microRNAs and long non-coding RNAs reinforces the functional similarities and provides further evidence of the equivalence of CMs derived from different pluripotent stem cell sources.

For more on the steady march of iPSCs to the clinic, keep reading the Stem Cells Portal.

References

  1. Chong, J.J., et al., Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 2014;510:273-7.
  2. Laflamme, M.A., et al., Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 2007;25:1015-24.
  3. Chin, M.H., et al., Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 2009;5:111-23.
  4. Narsinh, K.H., J. Plews, and J.C. Wu, Comparison of human induced pluripotent and embryonic stem cells: fraternal or identical twins? Mol Ther 2011;19:635-8.
  5. Lee, W.H., et al., Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Stem Cells 2017;35:2138-2149.
  6. Yellon, D.M. and S.M. Davidson, Exosomes: nanoparticles involved in cardioprotection? Circ Res 2014;114:325-32.