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hepatic stellate cells; Lama2; Lama5; liver stem cell niche; basement membrane, space of Dissé
Abstract:
The laminin α5 protein chain is an element of basement membranes and important to
maintain stem cells. Hepatic stellate cells (HSC) are liver-resident mesenchymal
stem cells, which reside in a quiescent state on a basement membrane-like structure
in the space of Dissé. In the present study, laminin α5 chain was detected in the
space of Dissé of normal rat liver. Since HSC are critical for liver regeneration and
can contribute to fibrosis in chronic liver diseases, the effect of laminins on HSC
maintenance was investigated. Therefore, isolated rat HSC were seeded on
uncoated polystyrene (PS) or PS coated with either laminin-521 (PS/LN-521) or
laminin-211 (PS/LN-211). PS/LN-521 improved HSC adhesion and better preserved
their retinoid stores as well as quiescence- and stem cell-associated phenotype,
whereas HSC on PS/LN-211 or PS developed into myofibroblasts-like cells. To
improve the homogeneity as well as the presentation of laminin molecules on the
culture surface to HSC, laminin-functionalized, gold-nanostructured glass surfaces
were generated. This approach further enhanced the expression of quiescenceassociated
genes in HSC. In conclusion, the results indicate that LN-521 supports the
quiescent state of HSC and laminin α5 can be regarded as an important element of
their niche in the space of Dissé.
