Characterization of human intestinal stromal cell lines: Response to cytokines and interactions with epithelial cells

The maintenance of the physiological homeostasis of the gut mucosa characte rized by continuous proliferation and differentiation processes results fro m epithelial-mesenchymal cell cross-talk. To set out stable and homogeneous models for the study of the (dys)regulation of various morphofunctional as pects, we established and characterized three clonal cell lines (C9, C11, a nd C20) derived from human duodenal mucosal connective tissue. We defined t he expression of (i) cytoskeletal proteins; (ii) basement membrane molecule s (laminins, collagen IV, nidogen) which have been shown formerly to be dep osited at the epithelial/mesenchymal interface in situ by the mesenchymal c ompartment; and (iii) soluble factors, HGF, and TGF beta 1. The three cell lines display common but also specific proliferative responses to cytokines (IL1 beta, IL2, IL8, TNF alpha, IFN gamma, TGF beta 1, and HGF). When cocu ltured with embryonic intestinal endoderms or with human colonic Caco2 or H T29 cancer cells, C9 versus C11 and C20 cell lines induced limited versus e xtensive growth of the associated epithelial cells. In addition C20 cells a llowed spreading of HT29 cells with the formation of a basement membrane at the heterologous interface. Morphogenesis obtained by intracoelomic grafts of associations comprising the mesenchymal cell lines and intestinal endod erms was also different among those composed of C9 cells or of C11 or C20 c ells. In conclusion, these data indicate that the mucosal connective tissue is heterogeneous and comprises several phenotypically different mesenchyme -derived cells whose equilibrium may be important in the gut homeostasis. T hese cells can now be used to define tissue-specific factors which may be i nvolved in the physiopathology of the intestinal epithelium. (C) 1999 Acade mic Press.