Biomedical Engineering Reference
In-Depth Information
7.2 Micropatterned Cocultures
Large organisms owe their ability to develop complex behaviors to the cooperation of multi-
ple cell types, each with a specialized function. It is of no surprise, then, that many cell types
function poorly when separated from their neighbors, which may secrete signals that regulate
expression of key genes involved in growth, proliferation, motility, and diferentiation, among
other processes. here is a reason why the body is made of multiple components, and separating
it into pieces is always a source of problems.
Certain cell types are more sensitive than others at being separated from their neighbors—
probably because certain tissues rely on the 3-D natural structure to perform their function
more than others. Hepatocytes (liver cells), which in the liver are surrounded not by one but by
many other cell types (endothelial cells, ibroblasts, and Kupfer cells), are notorious for losing
all their liver-speciic functions (e.g., albumin secretion, urea synthesis, p450 detoxiication,
etc.) within a couple of days of culture—unless they are cocultured with a second cell type (such
as ibroblasts). Neurons, which in the brain are surrounded by glial cells and whose long axons
and dendrites are severely damaged by the isolation process that reduces them temporarily to a
spherical cell, are extremely sensitive in culture and do not survive well unless kept in the pres-
ence of a “feeder layer” of
glial cells
.
Mehmet Toner's group at Harvard Medical School is credited for pioneering the concept
of micropatterned cocultures. he hope of the approach, depicted in
Figure 7.12
, is that by
reproducing some key elements of the cellular architecture found in vivo, one is restoring the
signaling present in vivo, thus enhancing the function observed with respect to the control
random cocultures. his group used microfabrication to optimize the liver-speciic functions in
hepatocyte-ibroblast cocultures.
7.2.1 Liver Cells
Mehmet Toner and colleagues found interesting trends in liver-speciic functions measured
from these micropatterned cocultures (see also Section 2.6.2.1 and
Figure 2.34
). To optimize
the amount of contact between the two cell types, they designed patterns with various hepa-
tocyte/ibroblast contact that had the same available surface for both cell types, as shown in
Figure 7.13
. (Fibroblasts that landed in between hepatocytes were neglected.) In these micropa-
tterned cocultures, unlike in a random coculture coniguration, the seeding density can be
speciied independently of the length of contact between the two cell populations. For example,
in the three patterns of
Figure 7.13
, the ratio of area available to ibroblasts versus area avail-
Random cocultures
Live
tissue
Microfabricated
cocultures
FIGURE 7.12
Random.and.micropatterned.cocultures.
