Embryonic Stem Cells or Induced Pluripotent Stem Cells? A DNA Integrity Perspective

Abstract

Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical research and medical applications. iPSCs were initially favorably compared to ESCs. This view was first based on ethical arguments (the generation of iPSCs does not require the destruction of an embryo) and on immunological reasons (it is easier to derive patient HLA-matched iPSCs than ESCs). However, several reports suggest that iPSCs might be characterized by higher occurrence of epigenetic and genetic aberrations than ESCs as a consequence of the reprogramming process. We focus here on the DNA integrity of pluripotent stem cells and examine the three main sources of genomic abnormalities in iPSCs: (1) genomic variety of the parental cells, (2) cell reprogramming, and (3) in vitro cell culture. Recent reports claim that it is possible to generate mouse or human iPSC lines with a mutation level similar to that of the parental cells, suggesting that "genome-friendly" reprogramming techniques can be developed. The issue of iPSC DNA integrity clearly highlights the crucial need of guidelines to define the acceptable level of genomic integrity of pluripotent stem cells for biomedical applications. We discuss here the main issues that such guidelines should address.

The HDAC Inhibitor LAQ824 Enhances Epigenetic Reprogramming and In Vitro Development of Porcine SCNT Embryos

“…Embryonic stem cells (ESCs) have greater therapeutic potential than iPSCs because they have fewer genetic and epigenetic defects [41]. Porcine SCNT is also a promising technology, with potential applications in regenerative medicine and xenotransplantation [2].…”

Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives

“…However, before clinical implementation of induced PSCs transplantation there is required to perform fundamental investigations related the specificity, efficiency, kinetics, and biological safety of novel methods of cell reprogramming. Despite results of controlled studies in this field are limited, novel approaches regarding improve and change the induced PSC process promise to be more successful than previous [31] . Currently there are some transcription factors (molecular factors, vectors, various small molecules) that might be useful for improving functionality of induced PSCs before replacement.…”

“…Results of the recently studies have been found that using transcription factors for trans-differentiation of induced PSC into patient-specific cells may open a new era of regenerative medicine. The use of different types of somatic cells with trans-differentiation technology is consider an important approach for improving plastic of induced PSC reprogramming and as serious extend of possibilities for increasing efficacy and biological safety of regenerative medicine [29,31] . Finally, irrespective several limitation of clinically-based evidences of implementation of transdifferentiation on routine clinical practice, it is required to accumulate efforts toward summarize of knowledge about novel method of induced PSC transcription.…”

Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for Growth Advantage

“…The reason for differences in the types of karyotypic abnormalities in iPSC versus ESC is yet unclear and it may be hypothesized that it is related to the methods used for reprogramming [15]. Furthermore, only a few studies have compared the frequency of genomic rearrangements in iPSC with respect to different methods of reprogramming [16].…”