Biomedical Engineering Reference
In-Depth Information
7.2.2 Lung Cells
Perhaps microluidic systems are most needed to model those organs in which two vascular-
izations meet each other—such as in the blood-brain barrier, the lung, the liver, and so on—
because traditional two-dimensional cell culture systems cannot mimic mass transport in the
third dimension (usually a porous membrane or cell fenestrations). In this area, one of the
most imaginative work has come from the laboratory of Shuichi Takayama at the University of
Michigan, who has developed a microluidic cellular model of the lung (
Figure 7.15
). Primary
human small airway epithelial cells (
SAECs
) are seeded on a porous polyester membrane con-
taining 400-nm pores (which mimics the in vivo basement membrane and limits transport
of solutes by difusion). he size of the microchannels (300 and 100 μm in width and height,
respectively) was chosen to recreate the dimensions of distal conducting airways and respira-
tory bronchioles. Once the SAECs form a conluent monolayer (in ~6 days), their apical surface
is exposed to an air-liquid interface (i.e., they are exposed to air), as shown in
Figure 7.15c
. his
system allows for studying how pathologic luid mechanical stresses (e.g., the propagation and
rupture of liquid plugs;
Figure 7.15d
and
e
) can induce injury of SAECs.
Building on Takayama's model, Don Ingber's group at Harvard University has presented a
“lung-on-a-chip” design, whereby the porous membrane and the whole epithelial cell layer can
be stretched to mimic the cyclic mechanical strain “seen” by lung cells (
Figure 7.16
). Stretching
is applied via two side vacuum channels (
Figure 7.16a
). In vivo, inhalation due to diaphragm
contraction results in distension of the alveoli (see
Figure 7.16b
); in this study, “inhalation” also
results in the stretching of the alveolar-capillary interface. his bioinspired microdevice shows
that cyclic mechanical strain accentuates toxic and inlammatory organ-level lung responses to
silica nanoparticles. Furthermore, mechanical strain enhances the uptake of nanoparticles by
epithelial and endothelial cells and stimulates their transport into the underlying microvascular
channel, an efect that is also seen in mouse lung in nanoparticle breathing experiments.
Upper
chamber
(a)
(b)
(c)
(f )
Culture media
Air
Epithelial
cell
Flow
Seeding
Porous
membrane
Flow
Membrane
Flow
(e)
Lower
chamber
Day 2
Plug
generator
Plug
(d)
Day 5
Rupture
FIGURE 7.15
A. microluidic. model. of. lung.. Scale. bars:. 150. μm.. (From. Dongeun. Huh,. Hideki.
Fujioka,.Yi-Chung.Tung,.Nobuyuki.Futai,.Robert.Paine.III,.James.B..Grotberg,.and.Shuichi.Takayama,.
“Acoustically.detectable.cellular-level.lung.injury.induced.by.luid.mechanical.stresses.in.microlu-
idic.airway.systems,”.
Proc. Natl. Acad. Sci. U. S. A.
.104,.18886-18891,.2007..Copyright.(2007).
National.Academy.of.Sciences,.U..S..A.)
