DEPARTAMENTO DE CIÊNCIAS DA VIDA ... - Estudo Geral

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only ones MSCs can differentiate into. It has been shown that the differentiation
potential of these cells covers cells with markers characteristic of the three germ layers
(ectoderm, mesoderm and endoderm), like cells similar to cardiomyocytes (Wang et
al., 2004), skeletal muscle cells (Conconi et al., 2006), endothelial cells (Wu et al.,
2007), hepatocytes (Lee et al., 2004; Anzalone et al., 2010) and neural-like lineages
(Weiss et al., 2003; Sanchez-Ramos et al., 2008).
Of particular interest for this thesis, is the neural-like differentiation of MSCs. It
was demonstrated that nestin-positive MSCs can differentiate into neuron-like cells
(Wislet-Gendebien et al., 2005) and probably the expression of this neuroectodermal
marker is related with the neuroepithelial origin of these cells (Takashima et al., 2007;
Mendez-Ferrer et al., 2010). Futher studies also showed that nestin-positive MSCs
were induced to a neural stem-like cell fate and then converted into oligodentrocyte
precursor-like cells (Zhang et al., 2010), reinforcing the idea that nestin-positive MSCs
have the capability to differentiate into neural-like lineages.
I.2. - Mechanotransduction and its implications in cellular fate
Mechanical forces are normally implicated in the regulation of many
physiologic and pathologic processes and are the basis of mechanotransduction.
Mechanical loading can induce hypertrophy and strengthening of muscles, tendons,
ligaments and bones, whereas prolonged exposure to weightlessness seems to make
the opposite, e.g. left early astronauts prone to bone fractures (Burkholder, 2007;
Duncan and Turner, 1995; Hattner and McMillan, 1968). Similar hypertrophic
thickening, but this time due to pathogenic symptoms, occurs in the heart with
unchecked hypertension, although in this case potentially dangerous consequences
may occur (Weber et al., 1989; Westerhof and O’Rourke, 1995). Differences in the
flow-induced shear stress on veins or arteries specify their endothelium differentiation
in part to become a venous or arterial phenotype, and certain regions are more
susceptible to inflammation due to the distribution of shear stresses within the arterial
tree, explaining the observed distribution of atherosclerotic plaques (Davies et al.,
1995; Garcia-Cardena et al., 2001). The contractile activity of cells generates
mechanical forces that drive physical changes in a developing embryo, but also are