Biomedical Engineering Reference
In-Depth Information
Hepatocytes
+Fibroblasts
Single-cell islands
100 µm
FIGURE 7.13
Micropatterned.hepatocyte/ibroblast.cocultures.of.various.sizes..(From.S.N..Bhatia,.
U.J..Balis,.M.L..Yarmush,.and.M..Toner,.“Probing.heterotypic.cell.interactions:.Hepatocyte.function.
in.microfabricated.co-cultures,”.
J. Biomater. Sci. Polym. Ed.
,.9,.1137,.1998..Figure.contributed.by.
Sangeeta.Bhatia.)
able to hepatocytes is 4:1 in all three patterns—but the amount of contact between the two cell
populations increases as the size of the islands decreases.
At least two liver-speciic functions (albumin production and urea synthesis) were seen to
improve with decreasing island size (see graph in
Figure 7.14
), and intracellular albumin stain-
ing revealed that the signal provided by the ibroblasts is of short range (see
Figure 7.14
). It was
also found that albumin production and urea synthesis, which were known to decay with time
in random cocultures, are sustained for lengthy periods of time (~2-6 weeks) in certain micro-
fabricated cocultures featuring the same cell-cell ratio as the random coculture. In addition, the
response of hepatic function to changes in ibroblast number was distinct from that attributed to
increased contact between hepatocytes and ibroblasts, suggesting that ibroblast number plays a
role in the modulation of hepatic function through homotypic ibroblast interactions. his work
suggests the possibility of building bioartiicial livers on the basis of highly eicient micropat-
terned liver cell cocultures.
Intracellular albumin
Day 1
Secreted albumin
8
7
6
5
4
3
2
1
0
Diameter [
µm]
36
µm
100
µm
490
µm
6800
µm
17800
µm
Day 6
3
5
7
9
11
Day 3
Day
Hepatocytes
Hepatocytes
Fibroblasts
Fibroblasts
FIGURE 7.14
Enhanced.liver.function.in.micropatterned.hepatocyte/ibroblast.co-cultures..(From.
S.N.. Bhatia,. U.J.. Balis,. M.L.. Yarmush,. and. M.. Toner,. “Probing. heterotypic. cell. interactions:.
Hepatocyte.function.in.microfabricated.co-cultures,”.
J. Biomater. Sci. Polym. Ed.
,.9,.1137,.1998..
Figure.contributed.by.Sangeeta.Bhatia.)
