Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 331

colonies, derived from murine and human embryonic stem cells, that
express Flk1 have also generated cardiac, endothelial and smooth muscle-
type cells (Kattman et al. , 2006; Moretti et al. , 2006; Yang et al. , 2008).
Whether the vascular cell-generating heterogeneous cell colonies that
express markers, such as CD34 and VEGFR2, overlap or are one and the
same requires investigation (Bai et al. , 2010).
Using a vascular cell differentiation system, ECs and mural cells were
derived from human embryonic stem cells (Sone et al. , 2007). The same
group employed these cells in vivo in a murine hind limb ischaemia model.
They reported that the ECs and mural cells worked best when transplanted
together at the correct stage of their differentiation. When the cells were
injected into the arterial circulation, blood fl ow to ischaemic limbs improved
after 42 days (Yamahara et al. , 2008). Transplanting mature vascular cells,
i.e. human endothelial progenitor cells from peripheral and umbilical blood,
were markedly less effective at improving ischaemia. Blood fl ow is thought
to have increased due to the structural contribution of the transplanted cells
as well as their paracrine effects. The use of embryonic stem cells would
thus have regenerative and tissue engineering applications. ECs derived
from human embryonic stem cells were transplanted into mice using Matri-
gel as a scaffold and contributed to the formation of blood vessels (Ferreira
et al. , 2007b).

12.6.3 Adult stem cells

Adult stem cells are a potential alternative autologous source of ECs and
SMCs for vascular tissue engineering applications. The ethical issues sur-
rounding the use of adult stem cells are less complex than in the case of
embryonic stem cells. The benefi ts of employing adult stem cells are offset
by their scarcity and their prolonged proliferation time in vitro .
The bone marrow is a rich source of tissue-specifi c stem and progenitor
cells. Endothelial progenitor cells form a subset of cells within the bone
marrow and relocate to the circulation in response to vascular pathology
and tissue ischaemia, where they differentiate into ECs. Although limited,
most of the current knowledge around endothelial progenitor cells entails
this cell-type's proliferation, recruitment, mobilisation and incorporation in
angiogenesis; see Fig. 12.3 (Rafi i and Lyden, 2003). There is still much
controversy surrounding the origin, isolation and effects of endothelial
progenitor cells (Deb and Patterson, 2010).
Multipotent adult progenitor cells, isolated from human bone marrow
and modulated in vitro , differentiated into cells which structurally and
functionally resembled SMCs (Ross et al. , 2006). These cells were examined
in detail to determine their suitability for potential vascular tissue engineer-
ing applications. The SMC-like cells expressed less telokin and

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γ -actin,