Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 326

Diffi culties arise with stem cells when one attempts to select the cells
which will have the most potential to differentiate into the required target
cell type to be examined or employed. Impediments to the use of embryonic
stems cells include, isolating homogeneous populations of differentiated
cells, and acquiring populations of terminally differentiated cells that are
capable of further proliferation (McCloskey et al. , 2006b). In addition,
having isolated a population of seemingly differentiated cells from a stem
cell source, these cells may not function as optimally as a mature cell type.
When compared with mouse aortic ECs harvested from thoracic aortas,
embryonic stem cell-derived ECs expressed fewer adhesion factors and von
Willebrand factor (vWF) (McCloskey et al. , 2006a). Although this was a
limited study which only employed immuno-histochemistry, it does raise
questions about the effi cacy and reliability of stems cells in tissue engineer-
ing applications. Essentially, stem cell-derived vascular cells, seeded into
the wall and onto the luminal surface of tissue engineered vascular grafts,
must be mature enough to survive and function within the rigorous cardio-
vascular system milieu.

12.6.1 Stem cells as a source of endothelial and vascular
smooth muscle cells
During embryogenesis in vertebrates, the endothelium is the fi rst tissue to
differentiate. ECs are crucial to the success of TEBVs. The search for
alternate sources of ECs was prompted by the limited availability of mature
ECs and their slow and fi nite proliferation potential. VSMCs are essential
for successful angiogenesis and blood vessel homeostasis (Conway et al. ,
2001). The incorporation of VSMCs into TEBVs is controversial as these
cells are not always easy to manipulate. The derivation of VSMCs from
stem cells has been successfully attempted using murine and human embry-
onic stem cells, adult stem cells and iPSCs (Chen and Lechleider, 2004;
Huang et al. , 2006; Moretti et al. , 2010; Ross et al. , 2006; Sinha et al. , 2004;
Xie et al. , 2007, 2009). The majority of knowledge, however, revolves
around the differentiation of stem cells into ECs.
The ideal SMCs, derived from adult stem cells, for deployment in a tissue
engineered vascular conduit should have the following functional charac-
teristics (Ross et al. , 2006):

￿ ￿ ￿ ￿ ￿

￿ If seeded into a scaffold, the ability to manufacture SMC-like
ECM, including collagen and elastin. These ECM components would
replace the scaffold with a stable structure possessing mechanical
integrity.
￿ A contractile phenotype enabling the cells to contract and relax
appropriately.