Derivation of Human Induced Pluripotent Stem Cell (iPSC) Lines and Mechanism of Pluripotency: Historical Perspective and Recent Advances

Abstract

Derivation of human embryonic stem cell (hES) lines in 1998 was not only a major technological breakthrough in the field of regenerative medicine; it also triggered a passionate debate about the ethical issues associated with the utilization of human embryos for derivation of hESC lines. Successful derivation of induced pluripotent stem cell (iPS) lines from human somatic cells with defined reprogramming factors by Shinya Yamanaka`s group in 2007 was another breakthrough that generated enormous excitement and hope for the development of donor-specific personalized cell replacement therapies (CRT) without the ethical dilemma associated with it. As we approach twentieth anniversary of derivation of hESC lines and the tenth anniversary of isolation of donor-specific iPSC lines, this manuscript summarizes the key advances in pluripotent stem cell (PSC) research field that led to derivation of human iPSC lines, different methodologies for derivation iPSC lines and characterization of the mechanism of reprogramming. We will also review progress towards generating donor-specific somatic cell lineages from iPSC lines, especially the functional immune cell lineages, and progress towards advancing these findings to the clinic. Finally, we will discuss the challenges, such as genome instability and inherent immunogenicity of hPSC lines that need to be addressed to develop safe and effective iPSC-based CRT.

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Abbreviations

hPS cells:

Human pluripotent stem cells

hES cells:

Human embryonic stem cells

iPS cells:

Induced pluripotent stem cells

EB:

Embryoid bodies

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Acknowledgements

Arvind Chhabra conceived and wrote the manuscript. Arvind Chhabra made the figures, in part using the Servier-Medical Art Slides. Author offers heartfelt gratitude to authors of the manuscripts that are cited here and many more that could not be included because of the space limitations. Author also thanks Deepika Batra and Feny Rasania for help in the preparation of the manuscript. This work was supported by grants from the State of Connecticut Regenerative Medicine Program (10-SCA-23 and 13-SCB-05).

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Chhabra, A. Derivation of Human Induced Pluripotent Stem Cell (iPSC) Lines and Mechanism of Pluripotency: Historical Perspective and Recent Advances. Stem Cell Rev and Rep 13, 757–773 (2017). https://doi.org/10.1007/s12015-017-9766-9

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Keywords

  • Human embryonic stem cells (hESC)
  • Human pluripotent stem cells (hPS)
  • Induced pluripotent stem cells (iPS). iPSC-based cell replacement therapies (CRT)