Title:Technological Overview of iPS Induction from Human Adult Somatic Cells
Volume: 13
Issue: 2
Author(s): Emilie Bayart and Odile Cohen-Haguenauer
Affiliation:
Keywords:
Human induced pluripotent stem cells, stem cells engineering, regenerative medicine, reprogramming methods, gene transfer systems, genetic instability
Abstract: The unlimited proliferation capacity of embryonic stem cells (ESCs) combined with their pluripotent differentiation
potential in various lineages raised great interest in both the scientific community and the public at large with hope
for future prospects of regenerative medicine. However, since ESCs are derived from human embryos, their use is associated
with significant ethical issues preventing broad studies and therapeutic applications. To get around this bottleneck,
Takahashi and Yamanaka have recently achieved the conversion of adult somatic cells into ES-like cells via the forced
expression of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. This first demonstration attracted public attention
and opened a new field of stem cells research with both cognitive – such as disease modeling - and therapeutic prospects.
This pioneer work just received the 2012 Nobel Prize in Physiology or Medicine. Many methods have been reported since
2006, for the generation of induced pluripotent stem (iPS) cells. Most strategies currently under use are based on gene delivery
via gamma-retroviral or lentiviral vectors; some experiments have also been successful using plasmids or transposons-
based systems and few with adenovirus. However, most experiments involve integration in the host cell genome with
an identified risk for insertional mutagenesis and oncogenic transformation. To circumvent such risks which are deemed
incompatible with therapeutic prospects, significant progress has been made with transgene-free reprogramming methods
based on e.g.: sendai virus or direct mRNA or protein delivery to achieve conversion of adult cells into iPS. In this review
we aim to cover current knowledge relating to both delivery systems and combinations of inducing factors including
chemicals which are used to generate human iPS cells. Finally, genetic instability resulting from the reprogramming process
is also being considered as a safety bottleneck for future clinical translation and stem cell-therapy prospects based on
iPS.