Induced differentiation and maturation of newborn liver cells into functional hepatic tissue in macroporous alginate scaffolds Academic Article uri icon

abstract

  • The present work explores cell cultivation in macroporous alginate scaffolds as a means to reproduce hepatocyte terminal differentiation in vitro. Newborn rat liver cell isolates, consisting of proliferating hepatocytes and progenitors, were seeded at high cell density of 125 × 106/cm3 within the scaffold and then cultivated for 6 wk in chemically defined medium. Within 3 days, the alginate-seeded cells expressed genes for mature liver enzymes, such as trypthophan oxygenase, secreted a high level of albumin, and performed phase I drug metabolism. The cells formed compacted spheroids, establishing homotypic and heterotypic cell-to-cell interactions. By 6 wk, the spheroids developed into organoids, with an external mature hepatocyte layer covered by a laminin layer encasing inner vimentin-positive cells within a laminin-rich matrix also containing collagen. The hepatocytes presented a distinct apical surface between adjacent cells and a basolateral surface with microvilli facing extracellular matrix deposit...

publication date

  • January 1, 2008