title: Gradients in the liver's extracellular matrix chemistry from periportal to pericentral zones: influence on human hepatic progenitors.
abstract: Embryonic mesenchymal feeders produce paracrine signals requisite for ex vivo survival and expansion of hepatic progenitors. The signals consist of a subset of soluble factors found in conditioned medium, and a subset of insoluble factors found in extracellular matrix that include collagens and basal adhesion molecules. We have identified key matrix components required for ex vivo maintenance of human hepatic progenitors produced by biologically active feeders. These components are similar to those found in zone 1 of the liver acinus (e.g., space of Disse) between layers of parenchyma and endothelia. Within these layers are transition chemistry matrix gradients, from zone 1 to zone 3. Use of purified zone 1 matrix components enables attachment and expansion of human hepatic progenitors independent of feeders. Cells aggregated into spheroid-like structures on laminin or spread into monolayers on type III or IV collagens. Contrastingly, a zone 3 matrix component, type I collagen, elicited growth arrest and differentiation. Another zone 3 matrix component, fibronectin, inhibited attachment. Use of specific matrix components, along with soluble paracrine signals from feeders, should enable one to maintain hepatic progenitors ex vivo without feeders and under wholly defined conditions.
authors.affiliation: Department of Cell and Molecular Physiology, Program in Molecular Biology and Biotechnology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. rmcclelland@admettechnologies.com
authors.forename: Randall
authors.initials: R
authors.lastname: McClelland
authors.forename: Eliane
authors.initials: E
authors.lastname: Wauthier
authors.forename: Josh
authors.initials: J
authors.lastname: Uronis
authors.forename: Lola
authors.initials: L
authors.lastname: Reid
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen; D005109:Extracellular Matrix; D006801:Humans; D007797:Laminin; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D019899:Paracrine Communication / Q000502:physiology*; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D007797:Laminin; D003094:Collagen