Hepatocyte Spheroid Self-Assembly
Cells isolated from many tissues self-organize
in vitro to form multicellular structures under suitable conditions.
Such a self-assembly being a manifestation of the process of tissue
organization, is useful for revealing invaluable clues regarding
the principles of tissue formation. The resulting self-organized
structures are often shown to promote the retention of architectural
and functional characteristics typical of the tissue of origin.
Studies on rat and porcine hepatocytes
have demonstrated that the cytological and functional differentiation
in culture are maintained and even enhanced when these cells self-assemble
into round three-dimensional aggregates, or spheroids. The development
of a structural configuration that resembles the native hepatic
tissue concomitant with the increase in liver-specific functions
is intimately related to the dynamic cytoskeletal organization.
The assembly process entails specific intercellular adhesions
and redistribution of cell-cell and cell-surface adhesion forces
through cytoskeletal reorganization.
Hepatocytes in their native environment
possess unique structural polarity in comparison to other epithelial
cells. They display two or three basal surfaces as well as apical
domains. The basal surface faces the liver sinusoid whereas the
apical domains are specialized for carrying out specific tasks
related for example to the trafficking of metabolites. The development
of similar structures has been observed in hepatocyte spheroids.
Tight junctions, bile-canaliculi-like structures and actin distribution
similar to the native liver tissue are observed in spheroids.
Characterization of the ultrastucture of hepatocyte spheroids
may provide significant insight regarding hepatocyte polarization
in vivo and in engineered tissue in vitro.