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The stem cells are the basic cells of our bodies
that have capacity to renew and multiply themselves indefinitely. There are
mainly two types of stem cells, embryonic stem cells (ESCs) and tissue-specific
(adult) stem cells. ESCs can be isolated from the ICM of the blastocyst at day
5 after fertilization. These cells can differentiate into any cell type of the
body given appropriate conditions, and proliferate infinitely as well. On the
other hand, adult stem cells that reside in most tissues can only be
differentiated into limited number of cell types of their tissue origin, and
have limited proliferation. The stem cells can be categorized into four groups,
totipotent, pluripotent, multipotent and unipotent stem cells, based on its
differentiation potency. Totipotent stem cells are the cells of embryo from
fertilized egg stage to the eight-cell stage, which can differentiate into both
embryonic and extraembryonic cell types. Pluripotent stem cells are the cells
of inner cell mass of the blastocyst that can differentiate into all embryonic
tissue except extraembryonic tissues. Multipotent stem cells are the cells that
differentiate into different types of cells but limited to its specific cell
lineage such as endoderm, ectoderm and mesoderm. Unipotent stem cells are the
cells with no pluripotency but self-renewal characteristic that differentiate
into only one type of cell such as adult stem cells.

first derivation of human embryonic stem cells (hESCs) in 1998 has introduced the
potential application of pluripotent and self-renewal characteristics of stem
cells in various area of scientific research, and has been provided as a tool
for studying human developmental processes, modeling diseases and drug
screening. However, derivation process of hESCs raised ethical concerns about
destroying human embryos. Moreover, use of hESCs for future clinical
application required life-long administration of immunosuppressive drugs. These
limitations of hESCs were overcome by discovery of patient-specific induced
plruipotent stem cells (iPSCs).

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2006, induced pluripotent stem cells (iPSCs) were discovered by Takahashi and
Yamanaka through reprogramming mouse skin cells. IPSCs resembled the
characteristics of self-renewal and pluripotency of hESCs. IPSCs were generated
from adult somatic cells by introducing specific transcriptional factors,
called Yamanaka factors, which induce changes in epigenetic conformation and
differentiation potential of the cells (Matthias). The factors reactivate dormant
pluripotency genes. Yamanaka and Takahashi identified a set of four
transcriptional factors, c-Myc, Oct3/4, SOX2 and Klf4, among 24 factors that
activate the pluripotency gene, Fbxo15 locus. This set of transcriptional
factors are introduced using retrovirus-mediated transduction and successfully
reactivated the Fbxo15 gene, reprogramming the fibroblast into iPSCs, however,
the resultant iPSCs showed incomplete promoter demethylation of embryonic stem
cell (ESC) regulators such as OCT4, and failed to differentiate into three germ
lines, thus expressing lower pluripotency compared with ESCs. Therefore, to
increase the level of pluripotency, another pluripotency gene, Nanog, is
selected and reactivated instead of Fbxo15, which resulted generation of iPSCs
that molecularly and functionally more resembles ESCs (Maherali). With this
implemented pluripotency gene, in 2007, the first human induced pluripotent
stem cells (hiPSCs) are generated from human fibroblasts by introducing a
cocktail of transcriptional factors, Oct3/4, SOX2, Nanog and Lin28, with the
same method used in reprogramming of mouse fibroblast. 

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