Induced pluripotent stem cells
Abstract :
iPSCs are a type of stem cell-like
embryonic stem cell, which are made from mature somatic cells These cells can
be differentiated into all body tissue [1]. The first paper was
published in 2006 by Takahashi and Yamanaka, after which many researchers
turned to this area for its importance [2]. A
Desirable feature of human iPSCs is the ability to acquire them from adult
patients to make a study on it and determine the cellular basis of human
disease [3].In 2007, scientist
Takahashi and his colleagues were able to apply the experiment on human
fibroblasts and that by introducing a few factors, human induced pluripotent
stem cells could be generated. At the same time, Yamanaka s group also reported
that reached the same result but with a different set of factors [4]. Some of these
factors are (Oct3 / 4, Sox2, Klf4, c-Myc) Which is highly reliable in the
production of induced stem cells, and their over-expression can induce
pluripotency in human somatic cells [5]. there are slight
differences in chromatin structure and gene expression between human Embryonic
cells and induced pluripotent stem cells, indicating that ES cells and iPSCs
are nearly identical cell types [6]. a short time ago,
it was assumed that human induced pluripotent stem cells (HiPSCs) would act
like their embryonic equivalent in respect to their tumorigenicity. However,
some evidence points to that there are important genetic differences between
these two cell types, which seem to affect their tumorigenicity [7]. With age, chronic
diseases begin to appear, especially cardiovascular and nervous diseases, some
of which are difficult to treat with a new drug. Patient induced stem cells can
easily treat these diseases [8]. Metabolism is
essential for every side of cell function, but the metabolism of iPSCs is still
mostly undetected, HiPSCs share a multicellular metabolic signature with ESCs, characterized by changes in metabolites
involved in cellular respiration [9]. Candidate compounds
are tested in the human or animal model, with often disappointing results. but,
some of these experiments achieve success, drugs such as the kinase inhibitor
sorafenib (Nexavar), and several drugs targeting G protein-coupled receptors,
such as olanzapine (Zyprexa) [10].
Reference :
[1] K et al., “Epigenetic
memory in induced pluripotent stem cells,” Nature, vol. 467, no. 7313,
pp. 285–290, 2010.
[2] D. A. Robinton and G. Q.
Daley, “The promise of induced pluripotent stem cells in research and therapy,”
Nature, vol. 481, no. 7381, pp. 295–305, 2012, doi: 10.1038/nature10761.
[3] P. Hou et al.,
“Pluripotent stem cells induced from mouse somatic cells by small-molecule
compounds,” Science (80-. )., vol. 341, no. 6146, pp. 651–654, 2013.
[4] S. Yamanaka, “Induced
pluripotent stem cells: past, present, and future,” Cell Stem Cell, vol.
10, no. 6, pp. 678–684, 2012.
[5] R.-J. Su et al.,
“Efficient generation of integration-free ips cells from human adult peripheral
blood using BCL-XL together with Yamanaka factors,” PLoS One, vol. 8,
no. 5, p. e64496, 2013.
[6] R. Lister et al.,
“Hotspots of aberrant epigenomic reprogramming in human induced pluripotent
stem cells,” Nature, vol. 471, no. 7336, pp. 68–73, 2011.
[7] U. Ben-David and N.
Benvenisty, “The tumorigenicity of human embryonic and induced pluripotent stem
cells,” Nat. Rev. Cancer, vol. 11, no. 4, pp. 268–277, 2011.
[8] M. Bellin, M. C. Marchetto,
F. H. Gage, and C. L. Mummery, “Induced pluripotent stem cells: the new
patient?,” Nat. Rev. Mol. cell Biol., vol. 13, no. 11, pp. 713–726,
2012.
[9] A. D. Panopoulos et al.,
“The metabolome of induced pluripotent stem cells reveals metabolic changes
occurring in somatic cell reprogramming,” Cell Res., vol. 22, no. 1, pp.
168–177, 2012.
[10] M. Grskovic, A. Javaherian,
B. Strulovici, and G. Q. Daley, “Induced pluripotent stem cells—opportunities
for disease modelling and drug discovery,” Nat. Rev. Drug Discov., vol.
10, no. 12, pp. 915–929, 2011.
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