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2018 ; 6
(ä): e4370
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Ten years of progress and promise of induced pluripotent stem cells: historical
origins, characteristics, mechanisms, limitations, and potential applications
#MMPMID29770269
Omole AE
; Fakoya AOJ
PeerJ
2018[]; 6
(ä): e4370
PMID29770269
show ga
The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in
2006 was heralded as a major breakthrough of the decade in stem cell research.
The ability to reprogram human somatic cells to a pluripotent embryonic stem
cell-like state through the ectopic expression of a combination of embryonic
transcription factors was greeted with great excitement by scientists and
bioethicists. The reprogramming technology offers the opportunity to generate
patient-specific stem cells for modeling human diseases, drug development and
screening, and individualized regenerative cell therapy. However, fundamental
questions have been raised regarding the molecular mechanism of iPSCs generation,
a process still poorly understood by scientists. The efficiency of reprogramming
of iPSCs remains low due to the effect of various barriers to reprogramming.
There is also the risk of chromosomal instability and oncogenic transformation
associated with the use of viral vectors, such as retrovirus and lentivirus,
which deliver the reprogramming transcription factors by integration in the host
cell genome. These challenges can hinder the therapeutic prospects and promise of
iPSCs and their clinical applications. Consequently, extensive studies have been
done to elucidate the molecular mechanism of reprogramming and novel strategies
have been identified which help to improve the efficiency of reprogramming
methods and overcome the safety concerns linked with iPSC generation. Distinct
barriers and enhancers of reprogramming have been elucidated, and non-integrating
reprogramming methods have been reported. Here, we summarize the progress and the
recent advances that have been made over the last 10 years in the iPSC field,
with emphasis on the molecular mechanism of reprogramming, strategies to improve
the efficiency of reprogramming, characteristics and limitations of iPSCs, and
the progress made in the applications of iPSCs in the field of disease modelling,
drug discovery and regenerative medicine. Additionally, this study appraises the
role of genomic editing technology in the generation of healthy iPSCs.