Biomedical Engineering Reference
In-Depth Information
Although the SMC-like cells generated from embryonic stem cells, using
the above-mentioned approaches, expressed contractile markers such as
α
SMA and SMMHC, the purity of the colonies were not convincingly
established. Undifferentiated cells within the SMC-like cell colony derived
from the embryonic stem cells induced teratocarcinomas
in vivo
(Martin,
1981). A number of approaches have been described to reduce the risk of
including undifferentiated cells in the cohort destined for
in vivo
and
in vitro
investigation. Ensuring the embryonic stem cells are differentiated
before transplantation is effective but not absolute (Barberi
et al.
, 2003).
Undifferentiated cells have been demonstrated to contaminate embryoid
bodies up to 28 days after the commencement of differentiation. These
undifferentiated cells were extracted by protracted 'negative selection'
lasting at least three days (Sinha
et al.
, 2006).
In mammals, the transforming growth factor beta (TGF
) superfamily
comprises approximately 40 multifunctional proteins. These proteins mod-
ulate the proliferation, differentiation, apoptosis, adhesion and migration
of various cell types. TGF
β
has a comprehensive infl uence on physiological
processes, including within the cardiovascular system (Euler-Taimor and
Heger, 2006; Redondo
et al.
, 2007). TGF
β
family members are subdivided
into two groups according to their interaction with receptors and the activa-
tion of downstream small mother against decapentaplegic (SMAD) tran-
scription factors (Bai
et al.
, 2010; Massague and Chen, 2000). Bone
morphogenic proteins (BMPs) constitute one group while the other group
comprises TGF
β
, activin and nodal.
Although the signalling pathways implicated in the differentiation of
embryonic stem cells have yet to be fully investigated, an intriguing insight
was provided by Sinha
et al.
(2004). Cells expressing markers of fully dif-
ferentiated SMCs, such as
β
SMA, Smoothelin-B and SMMHC, were
derived from murine embryonic stem cells, in an
in vitro
system. The SM2
subtype of SMMHC, a particular marker of well-differentiated SMCs, was
increasingly expressed in a time-dependent manner. On inhibiting the
TGF
α
-SMAD signalling pathway the expression of these markers was
signifi cantly reduced. Different components of the TGF
β
β
1-SMAD signal-
SMA and SMMHC. The
activity of the SMA promoter required both SMAD2 and SMAD3 while
only SMAD2 was necessary for SMMHC promoter activity (Sinha
et al.
,
2004).
Human embryonic stem cells that express CD34, the EC and haemato-
poietic cell surface marker, are heterogeneous, generating ECs and SMCs
(Bai
et al.
, 2010; Ferreira
et al.
, 2007b; Wang
et al.
, 2007). BMP2, BMP4 and
BMP7 have been implicated in the derivation of ECs and SMCs from
human embryonic stem cells that express CD34 (Bai
et al.
, 2010). Further
investigation of the exact signalling mechanism involved is necessary. Cell
ling pathway were involved in the expression of
α
Search WWH ::
Custom Search