Laminin-521 promotes quiescence in hepatic stellate cells

Laminin a5 is an important componentof basement membranes and essential to maintain stem cell characteristics.Since hepatic stellate cells (HSC) were previously described as mesenchymalstem cells, the effect of different... [ view full abstract ]

Laminin a5 is an important componentof basement membranes and essential to maintain stem cell characteristics.Since hepatic stellate cells (HSC) were previously described as mesenchymalstem cells, the effect of different laminins on the maintenance of isolated HSCwas investigated. Therefore, primary rat HSC were seeded on differentlaminin-coated surfaces (laminin-211, laminin-521) and uncoated polystyrene. Laminin-521improved HSC adhesion significantly compared to laminin-211 and polystyrene asanalyzed four hours after cell isolation. During one week of culture underserum-free conditions, HSC had lost almost all retinoid-containing lipiddroplets and developed into fibroblast-like cells on laminin-211 andpolysterene. In contrast, HSC cultured on laminin-521 increased in size, but showeda homogeneous morphology similar to freshly isolated HSC and retained theirretinoid droplets. Moreover, the expression of quiescence markers such as glialfibrillary acidic protein, Sparc like protein-1, lecithin retinolacyltransferase and notch1 was significantly higher in HSC on laminin-521 comparedto those cultured on laminin-211 and uncoated polystyrene. In support of this,activation markers like a-smooth muscle actin, collagen I, collagen IV and notch3were down-regulated, but the expression of stem cell markers such as growth anddifferentiation factor-3, CD133 and paired-like homeodomain transcriptionfactor-2c were up-regulated in HSC on laminin-521 compared to cells on laminin-211and polystyrene. In conclusion, these results suggest that laminin-521 promotesthe quiescent state in isolated HSC and laminin a5 could represent animportant element of their stem cell niche in the space of Dissé.