Biomedical Engineering Reference
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phosphate) nanofiber scaffold promoted the mechanical stability of
hepatocytespheroidswithsmallerbulkandanintegratedspheroid-
nanofiberconstruct.Recently,Feng
etal
.
47
preparednanofibrousGC
scaffolds by electrospinning. The results showed that hepatocytes
cultured on a GC nanofibrous scaffold formed stably immobilized
3Dflataggregatesandexhibitedsuperiorcellbioactivitywithhigher
levelsofliver-specificfunctionsthan3Dspheroidaggregatesformed
on GC films.
21.5.2
Coculture
It is already reported that coculture of hepatocytes with other types
ofcells as thefeeder cells can restore theliverfunctionandregulate
cell growth, migration, and/or differentiation,
29
although the exact
mechanismshavenotbeenelucidatedyet.Thismayinvolvethecell-
cell direct interactions between hepatocytes and feeder cells and
the soluble factors from the feeder cells because the cell-cell con-
tact interaction is important in the maintenance of hepatocytes.
50
Most commonly used feeder cells are epithelial- and fibroblast-
like cells.
51
Human hepatocytes cocultured with human biliary
epithelial cells restored the synthetic and metabolic liver function,
ammonia detoxification, cytochrome P450 function, and protein
expression and secretion.
52
Coculture of hepatocytes with fibrob-
lasts improved the hepatocytes function and lifespan.
53
Seo
et al
.
54
reported that the stabilized liver-specific functions
such as albumin synthesis, ammonia elimination, and cytochrome
P450activityofhepatocytescoculturedwithhepatocytesinthealgi-
nate/GCscaffoldand3T3fibroblastswereenhancedcomparedwith
those monocultured withhepatocytes, as shown in Fig. 21.4.
Coculture of rat hepatocytes with sinusoidal cells gave cultures
to survive longer with greater retention of the ultrastructural mark-
ersdistinctiveforallofthesecelltypes.
55
Therathepatocytescocul-
tured with 3T3-J2 murine fibroblasts retained their synthetic and
detoxification functions on a long-term basis.
56
The rat hepatocytes
viability cocultured with bone marrow cells were maintained as
long as 21 days, while the hepatocytes culture alone could only be
maintained for 7-10 days.
57
Also, the liver functions of the hepa-
tocytes were increased under the coculture with mouse embryonic
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