Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 324

promoted as a panacea by some groups, their effi cacy is still being
elucidated.

12.5.2 Vascular smooth muscle cells

VSMCs are strategically positioned within the arterial media and possess
mechano-sensing and chemo-sensing capabilities. These cells modulate
blood vessel tone and diameter which in turn infl uences blood pressure and
hence tissue perfusion. Cardiovascular pathology, like atherosclerosis
and intimal hyperplasia, partly develops through the infl uence of VSMCs.
VSMCs are inherently plastic, never attaining a terminal phenotype (Halka
et al. , 2008). Instead, phenotype is derived as a consequence of environ-
mental signals such as stretch, functional requirements such as repair after
vessel injury and the long-term maintenance of blood pressure (Birukov
et al. , 1995; Owens, 1995). Mature, differentiated VSMCs express protein
markers indicating their contractile ability such as alpha smooth muscle
actin (

SMA), smooth muscle myosin heavy chain (SMMHC), h 1 -calponin
and SM22

α

. Immature, poorly differentiated VSMCs proliferate, migrate
and manufacture ECM (Owens, 1995).
VSMC plasticity exemplifi es their heterogeneous nature. Morphological
and functional variability of SMCs has been reported in vivo and in vitro
(Archer et al. , 1996; Frid et al. , 1997a, b). Mature SMCs harvested from
different organs as well as those obtained from different locations of the
same organ demonstrated differences in morphology, contractility, prolif-
eration, ECM synthesis, response to growth factors and expression of con-
tractile proteins (Daemen and De Mey, 1995; Frid et al. , 1997a; Halayko
et al. , 1999; Majack et al. , 1996; Topouzis and Majesky, 1996). The existence
of 'tissue-district' specifi c heterogeneity of VSMCs harvested from two
locations within the same arterial tree was also recognised. This phenom-
enon was reported in VSMCs harvested from smaller arteries, i.e. less than
90

α

￿ ￿ ￿ ￿ ￿

m internal diam-
eter, of rats (Nakamura et al. , 1998). VSMCs are heterogeneous whether
they are obtained from healthy or diseased vessels. Within healthy vessels,
distinct VSMC subpopulations exist within the same segment of human
tunica media (Li et al. , 2001). In vessels altered by atherosclerosis and
intimal hyperplasia, intimal VSMCs are considerably different from those
in the media as they are poorly differentiated, enabling them to synthesise
components necessary for the remodelling and restructuring of the injured
vessel (Majack et al. , 1996; Shanahan and Weissberg, 1998).
The source and management of VSMCs before they are incorporated
into a tissue engineered blood vessel need to be carefully considered.
Attempts to consistently and successfully manipulate VSMC phenotype
prior to their inclusion into the graft has proved diffi cult. There are

μ m internal diameter, and larger arteries, i.e. 800-900 μ