摘要：SummaryIt is still a challenge for synthesizing ‘cellular niche-mimics’in vitrowith satisfactory reproducibility and fidelity to recreate the natural niche components (e.g., extracellular matrices and soluble factors) for stem cell cultivation. Inspired by the massive amplification of hepatic progenitor cells during liver fibrosisin vivo, here we optimized thein vitroliver 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 angiogenesis 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 quantitative proteomics which exhibited advantage over Matrigel for multi-passaged HB expansion. The pathology-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.Graphical abstractDisplay OmittedHighlights•Fibrotic niches were constructed by 3 hepatic cell lines plus 4 profibrotic factors•NE was produced by enzymatic digestion using pepsin and DNase•Collagen III, IV, IL-17, IL-18, and M-CSF resolved from NE promoted HBs expansionTissue engineering; Biomimetics; Stem cells research
