Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 327

ES cells

Mesoderm

Cardiovascular
progenitor cells

Haemangioblasts

Vascular
progenitor cells

Cardiomyocytes

Haematopoietic
progenitor cells

SMC
(pericytes)

EPC

Blood vessels

12.2 Human embryonic stem cells may act as a source of vascular
cells. Both haematopoietic cells and endothelial progenitor cells
(EPCs) are derived from haemangioblasts. The origins of smooth
muscle cells (SMCs) are dependent on the location in the embryo.
Vascular progenitor cells can further differentiate into mural cells, i.e.
SMCs and pericytes, and endothelial cells. EPCs may transdifferentiate
into SMCs during vessel formation. EPCs from cardiovascular
progenitor cells may potentially give rise to haematopoietic progenitor
cells. Reprinted by permission from Macmillan Publishers Ltd: Gene
Therapy (Bai and Wang) copyright (2008).

12.6.2 Embryonic stem cells

Embryonic stem cells are pluripotent because they can differentiate into
any cell line in vivo once introduced into a blastocyst (Bradley et al. , 1984).
Embryonic stem cells harvested from mice, primates and humans have
been investigated as a source of ECs; see Fig. 12.2 (Bai and Wang, 2008).
Embryonic stem cells that are cultured in a three-dimensional environment
form three-dimensional cell aggregates called embryoid bodies which, once
formed, proceed to differentiation (Doetschman et al. , 1985). Within mice,
a precursor cell population, called haemangioblasts, which show potential
for EC differentiation, have been identifi ed within embryoid bodies (Risau
et al. , 1988). However, haemangioblasts also differentiate into haematopoi-
etic cells (Wang et al. , 2004; Wiles and Keller, 1991; Zambidis et al. , 2005).
Great care would need to be taken to ensure that the appropriate cells are
selected for EC applications. Questions have been raised about the safety
of employing human embryonic stem cells to solve clinical problems. The
cells obtained and processed must be purifi ed, completely differentiated
and be immunologically tolerated when implanted. In addition, undifferen-
tiated human embryonic stems cells have teratogenic potential and epigen-

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