Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 336

VEGF alone, Flk1 positive cells differentiate into venous ECs. However,
with activation of the cyclic adenosine monophosphate (cAMP) pathway,
EC numbers increased and arterial ECs were identifi ed (Yurugi-Kobayashi
et al. , 2006). As well as being generated from embryonic stem cells, pluripo-
tent isl1 positive cells were also derived from human and mouse iPSCs,
without the formation of teratoma (Moretti et al. , 2010). Adult vascular
cells aside, mesenchymal stem cell-like cultures were isolated from human
iPSCs and were deployed in an acute ischaemia murine model. Twenty-one
days after injecting these generated cells into the muscle tissue surrounding
the excised segment of femoral artery, the physiological function of the
ischaemic limbs had improved. Enhanced muscle regeneration was also
demonstrated. The effi cacy of the mesenchymal stem cells derived from
iPSCs at salvaging the limbs from acute ischaemia was even better than
adult mesenchymal stem cells (Lian et al. , 2010).
Ideally, the vascular cells intended for tissue engineering applications
would be autologous. Most patients requiring bypass surgery and hence a
manufactured conduit would, by implication, have a diseased CVS. The
cells harvested from these patients would therefore run a risk of being
unhealthy, fragile and unsuitable for the robust nature of the arterial cir-
culation. The possibility of generating iPSCs from humans with disorders
has been investigated (Park et al. , 2008a). Although patients with cardio-
vascular pathology were not examined, this group's approach may be
employed to generate iPSCs from diseased arteries. These iPSCs may aid
in discovering drug therapy and other techniques to positively manipulate
diseased cells prior to their use in tissue engineered constructs (Yu et al. ,
2007). A limiting factor to the acute clinical use of this technique is the time
required to generate and reprogram the iPSCs generated from diseased
tissue (Park et al. , 2008b).

12.6.5 Employing stem cells in vascular tissue engineering

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Although stem cells have been demonstrated to differentiate into vascular
cells which then contribute to angiogenesis, these cells have not been
employed in engineered vascular conduits. They are, however, considered
to be the potential source of cells for the 'next generation' of vascular grafts
(Bu et al. , 2009). Apart from their differentiation into vascular cells, mes-
enchymal stem cells are thought to positively infl uence cardiovascular
repair through secreting anti-infl ammatory factors (Lee et al. , 2009).
In order to increase short and medium-term patency of synthetic grafts,
endothelialisation of the scaffold is encouraged by some groups (Anderson
et al. , 1987; Niklason et al. , 1999). As the sources of adult ECs are limited
and their propagation is diffi cult with variable rates of success, stem cells
have been investigated as an alternative. Little is known about the in vitro