Biomedical Engineering Reference
In-Depth Information
and exhibited some of the characteristics of mesenchymal cells.
35
The loss of apical-basal polarity and the gain of front-back polar-
ityisamorphogeneticprocesscalledEMT.EMTplaysanimportant
role in embryonic development
36
and a number of diseased states,
including fibrogenesis
37
,
38
and tumor metastasis.
39
A recent study
described that hepatocytes cultured on dried collagen undergo
EMT and become resistant to transforming growth factor-
β
(TGF-
β
)-induced apoptosis.
40
An
in vivo
study showed TGF-
β
1-induced
alveolar epithelial cell mesenchymal transition, which is mediated
by matrix protein fibronectin but not laminin/collagen mixtures.
41
Therefore,EMTmustbewellcontrolledinengineeringepithelialtis-
sues by providing appropriate ECM molecules orgrowth factors.
It is now known that ECM-mediated cell morphological change
selectively stimulates gene transcription. The expression of albu-
min, a liver-specific gene, is increased when hepatocytes grown
on an appropriate ECM substratum exhibit cuboidal, differenti-
ated cell morphology.
42
Tensile property of the substratum appears
critical in regulating cell shape and differentiation. Collagen gel
promotes hepatocyte differentiation, while dried nongel collagen
promotes de-differentiation.
42
The formation of epithelial polarity
is accompanied by proper functions. One of the major liver func-
tions is transcellular bile secretion, which is driven by the polar-
ized expression of distinct transport systems on the apical and
basaldomainsofhepatocytes.Incholestaticliverinjury,hepatocytes
becomede-differentiatedandlosetheircharacteristicsurfacetrans-
port polarity.
43
,
44
24.2.3
Other Physical Factors: Biomechanics and
Microfluidics
The ECM contains collagen fibers that resist tension and compres-
sion. While the epithelial sheet itself is a two-dimensional (2D)
structure, the whole tissue microenvironment is 3D. The combined
architecture of the basal membrane and ECM presents cells with 3D
topographical cues that include surface roughness on the nano- and
microscale,
45
curvature both at the micro- and macroscale,
46
and
isotropy, as in the parallel or random alignment of underlying col-
lagen fibers.
46
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