Hydrogel-Based Microfluidic Cell Culture 91
testing to give predictive data during further in vivo testing, the cells in culture
must mimic as closely as possible the in vivo behavior. Thus, drugs developed
using a monolayer screening system may not have the same activity against solid
tumors.
10
Currently, several three-dimensional cell culture systems are already used
in tumor and normal cell research.
9
Multicellular spheroids, in which spherical
aggregates are grown in suspension, are used to investigate tumor cell metabolism.
Cellular multilayers, in which layers of cells are cultured on porous membranes,
are used in studies of drug transport. Established 3-D culture methods used to
study drug penetration in tumors include multicellular spheroids, which are cell
aggregates typically suspended in rotating flasks, or spinner culture.
11
In collagen
cultures, a solid tumor specimen is embedded in a rat tail collagen gel, in order
to maintain the three dimensional structure. Multilayered cell cultures (MCCs)
feature thick layers of cells grown on permeable support membranes.
12
In one
configuration, the MCC separates two reservoirs which contain stirred media; the
drug is added to one reservoir and drug penetration through the thick ( 200 μm)
layer of cells is measured by sampling from the second reservoir.
13
5.1.3 Microscale Cell Culture Using Hydrogels
Current trends aim to culture cells in a mic roscale three-dimensional environment
that more closely mimics the natural extracellular environment.
15
Miniaturization
and spatial control are two goals addressed in microfluidic cell culture systems.
First, miniaturization permits more precise control of the microenvironment,
such as gradients in soluble factors. Gradients in biomolecules are essential
they guide cell growth, migration, and differentiation.
16
In Petri dishes, secreted
molecules are quickly dispersed over the entire bulk volume, and this loss of
Figure 5.1. A cell in a three-dimensional culture forming links with the scaffold.
2
For color
reference, see page 260.
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