Local remodeling of synthetic extracellular matrix microenvironments by co-cultured endometrial epithelial and stromal cells enables long-term dynamic physiological function

摘要: Mucosal barrier tissues, comprising a layer of tightly-bonded epithelial cells in intimate molecular communication with an underlying matrix-rich stroma containing fibroblasts and immune cells, are prominent targets for drugs against infection, chronic inflammation, other disease processes. Although human vitro models such barriers needed mechanistic studies drug development, differences extracellular matrix (ECM) needs stromal hinder efforts to create models. Here, using the endometrium as example mucosal barrier, we describe synthetic, modular ECM hydrogel suitable 3D functional co-culture, featuring components that can be remodeled by respond dynamically sequester local cell-secreted characteristic each cell type. The synthetic combines peptides off-the-shelf reagents is thus accessible biology labs. Specifically, first identified single peptide initial attachment both endometrial 2D semi-empirical screen. Then, co-culture system cultured on top gel-encapsulated show inclusion ECM-binding hydrogel, along integrin-binding peptide, leads enhanced accumulation basement membrane beneath more fibrillar collagen assembly over two weeks culture. Importantly, co-cultures composed either lines or primary displayed hormone-mediated differentiation assessed morphological changes secretory protein production. A multiplex analysis apical cytokine growth factor secretion comparing revealed strikingly different patterns, underscoring importance cell-cell networks. In summary, define "one-size-fits-all" enables long-term, physiologically responsive format.