Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 333

suggesting a closer resemblance to vascular rather than visceral SMCs. As
the adult progenitor cells differentiated and became more like VSMCs,
they expressed markers of contractility in the correct chronological order.
Once the SMC-like cells were passaged, they strongly assumed the features
of contractile VSMCs and lost their ability to express factors appropriate
to other cells such as ECs. As expected, TGF 1 was confi rmed to be very

infl uential in initially committing and then differentiating the multipotent
bone marrow-derived cells to SMCs (Ross et al. , 2006; Sinha et al. , 2004).
Not only did the SMC-like cells possess L-type calcium channels enabling
them to contract appropriately, but they also responded appropriately to
agonists and antagonists in vitro . When the generated SMC-like cells were
seeded into a three-dimensional fi brin gel environment, the cells replaced
the fi brin with collagen. Although histologically detectable elastin was not
manufactured, the cells expressed tropoelastin in the presence of PDGF-BB
when mechanically stimulated by cyclic strain for three weeks (Ross et al. ,
2006). Subjecting VSMCs to cyclic strain in vitro can induce a synthetic or
contractile phenotype depending on the magnitude and duration of the
applied force, the system used and the source of VSMCs examined (Birukov
et al. , 1995; Hishikawa et al. , 1994; Reusch et al. , 1996). Ross et al. suggested
that elastin synthesis may be enhanced through prolonged mechanical
stimulation, the inclusion of cytokines such as BMP and FGF. The
elastic lamina is located between the tunicae intima and media, which
are predominantly populated by ECs and VSMCs respectively. With
the latter in mind, Ross et al. suggested that co-culturing the SMC-like
cells with ECs may amplify elastogenesis (Ross et al. , 2006). This study
demonstrated that SMCs generated from adult stem cells are structurally
and functionally analogous to those derived from embryonic stem cells.
SMCs derived from adult stem cells would thus be a viable autologous
source of SMCs for deployment in engineered vascular conduits (Ross
et al. , 2006).
This knowledge may be used in developing techniques for employing
endothelial progenitor cells in tissue engineered vascular conduits. A com-
bination of endothelial progenitor cells and ECs was isolated and charac-
terised from peripheral blood and seeded onto unique nanocomposite
grafts. A confl uent cell layer was achieved after 14 days which maintained
its integrity for 35 days (Punshon et al. , 2008).
Distinct side populations of stem cells can also act as a source of
circulating ECs; see Fig. 12.3 (Rafi i and Lyden, 2003). These side popula-
tions are thought to occur in the parenchyma of the systemic vasculature
and organs as well as tissue of mesenchymal origin such as skeletal
muscle. Vascular progenitor cells within skeletal muscle are supplied
by bone marrow reserves but possess a distinct phenotype (Majka et al. ,
2003).

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