Biomedical Engineering Reference
In-Depth Information
exploited (Okita et al.
2008
; Stadtfeld et al.
2008
). The most promising strategy
toward the clinical application of iPS cells is the direct delivery of the repro-
gramming factors as recombinant proteins instead of DNA, which has been
demonstrated very recently to be feasible in both mouse and humans and which
may decrease the possibility of oncogenic transformation of these iPS cells (Kim
et al.
2009a
; Zhou et al.
2009
). Nevertheless, germline-derived stem pluripotent
stem cells, iPS cells and ES-like cells should all be regarded as good model systems
to study the reprogramming process involved in the reacquisition of pluripotency.
The comparison between these systems can shed light on the underlying mecha-
nisms of pluripotency and on why germline cells are able to be reprogrammed to
pluripotency simply by the culture environment whereas somatic cells require the
delivery of cocktails of pluripotency-related factors.
2.8
Conclusions
The spontaneous conversion of unipotent germ cells into pluripotent ES-like cells
constitutes an ideal model with which to unravel the mechanisms necessary to
switch a lineage-committed cell into a pluripotent cell. While the pluripotent stem
cells derived from conversion of SSCs produced in different laboratories all share
several major characteristics with ES cells, including their ability to self-renew and
differentiate into many cell types, there are potentially important and revealing
distinctions (Kanatsu-Shinohara et al.
2008b
). Elucidation of these differences
could reveal the answer to the intriguing question of whether more than one set of
signals can lead to the pluripotent phenotype. Functional data indicate that ES-like
stem cells derived from the testis represent at least a good research tool for probing
the acquisition of pluripotency and perhaps even a viable alternative to ES cells and
iPS cells for
in vitro
production of tissues for use in regenerative applications.
However, extensive work needs to be done to improve the efficiency of production
of ES-like cells, as well as to demonstrate their safety, before they can be imple-
mented in clinical trials.
One might hypothesize that the reason why SSCs can convert to pluripotent cells
spontaneously is that they are the only adult cells that maintain expression of the
most important pluripotency factor OCT4. In this scenario their conversion to pluri-
potent cells would just simply follow the same processes that are involved in the
conversion of somatic cells in iPS cells. In fact, it has already been demonstrated
that somatic cells that express endogenously some of the pluripotency factors (like
neural stem cells) can be reprogrammed by the expression of only the missing ones
(Kim et al.
2009b
). However, at the present stage it cannot be excluded that the set
of molecular changes that take place to convert a SSC to a pluripotent cell could be
different from those necessary to convert a somatic cell to a pluripotent stem cell.
We believe that the comparison of the two conversion processes at the molecular
level would shed light on the basic requirements for pluripotency as well as on how
many possible pathways exist to regain pluripotency after differentiation.
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