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Semino, C.E. et al.

Semino, Merok, Crane, Panagiotakos, Zhang,

Functional differentiation of hepatocyte-like spheroid structures from putative liver progenitor cells in three-dimensional peptide scaffolds.

We investigated the ability of a new type of biological material, the self-assembling peptide scaffold, to foster tissue-like function by a putative adult rat hepatocyte progenitor cell line, Lig-8. In conventional adherent petri-dish cultures, Lig-8 cells divide exponentially, express markers for definitive endoderm HNF3 beta and hepatocyte lineage, including CK8 and alpha-fetoprotein, but lack expression of mature hepatocyte markers. However, in the three-dimensional peptide scaffold cultures, Lig-8 exhibits non-exponential cell kinetics, acquires a spheroidal morphology, and produces progeny cells with mature hepatocyte properties. The differentiated progeny cells display expression of transcription factor C/EBP alpha and several other indicators that suggest hepatocyte maturation, including binucleation, up-regulation of albumin, and expression of cytochrome P450s CYP1A1, CYP1A2, and CYP2E1. Moreover, all three cytochrome p450 enzyme activities are induced using 3-methylcholanthrene in these spheroids. These results suggest that a designed biological material may provide a conducive microenvironment in which putative adult progenitor cells differentiate into functional hepatocyte-like spheroid clusters. This bioengineered scaffold system provides a better physiological approach to "progenitor cell differentiation" for future biomedical and pharmaceutics applications.[1]

References

Functional differentiation of hepatocyte-like spheroid structures from putative liver progenitor cells in three-dimensional peptide scaffolds. Semino, C.E., Merok, J.R., Crane, G.G., Panagiotakos, G., Zhang, S. Differentiation (2003) [Pubmed]

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