Synthetic liver fibrotic niche extracts achieve in vitro hepatoblasts phenotype enhancement and expansion

It is still a challenge for synthesizing 'cellular niche-mimics' in vitro with satisfactory reproducibility and fidality to recreate the natural niche components (e.g., extracellular mat:Ices and soluble factors) for stem cell cultivation. Inspired by the massive ampnication of hepatic progenitor cells during liver fibrosis in vivo, here we optimized the in vitro liver fibrotic niches and subsequently harvested their bioactive ingredients as niche extracts (NEs). The fibrosis-relevant NE marginally outperformed Matrigel for phenotype maintenance of human embryonic stem cell (hESC)-derived hepatoblasts (HBs) and recapitulation of the pathological angiogcnesis of hESC-derived endothelial cells both in 2D culture and 3D liver organoids. Finally, defined NE components (i.e., collagen III, IV, IL-17, IL-18 and M-CSF) were resolved by the quantative proteomicsr Lich exhibited advantage over Matrigel for multi-passaged HB expansion. The patho'ogy-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.

Automated summary

The challenge of synthesizing 'cellular niche-mimics' in vitro with satisfactory reproducibility and fidelity to recreate natural niche components for stem cell cultivation remains. Inspired by liver fibrosis-induced amplification of hepatic progenitor cells, researchers optimized fibrotic niches in vitro and harvested bioactive ingredients as niche extracts. These extracts outperformed Matrigel in maintaining human embryonic stem cells and replicating pathological angiogenesis, providing innovative strategies for discovering optimal cellular niche compositions.