Human hepatoblast phenotype maintained by hyaluronan hydrogels.
Human hepatoblasts and hepatic stem cells, pluripotent hepatic progenitors that give rise to hepatocytes and biliary cells, were isolated from fetal livers and found to express hyaluronan receptors (CD44) in both the freshly isolated cells and after culture. This implicates an in vivo connection to hyaluronan (HA), an embryonic matrix component, as a candidate 3-dimensional (3-D) scaffold for hepatic progenitor cell expansion and/or differentiation. To assess HAs as scaffolds, hepatoblasts and hepatic stem cells were seeded into HA hydrogels with a serum-free, hormonally defined medium tailored for expansion of hepatic progenitors. Cell aggregates formed within the HA hydrogels and remained viable, proliferative, and demonstrated a stable phenotype intermediate between that of hepatic stem cells and hepatoblasts throughout more than 4 weeks of culturing, with little evidence of lineage restriction towards either hepatocytic or biliary pathways. The phenotype consisted of stable co-expression of both hepatocytic and biliary markers such as biliary-specific cytokeratin, CK19, low levels of expression of albumin, and urea synthesis. HA hydrogels are ideal as 3-D scaffolds for pluripotent hepatic progenitors and should be useful for generating cells to be used in bioartificial livers or tissue engineered liver grafts.
Turner
William S
WS
Department of Biomedical Engineering, UNC School of Medicine, Chapel Hill, North Carolina 27599, USA.
Schmelzer
Eva
E
McClelland
Randall
R
Wauthier
Eliane
E
Chen
Weiliam
W
Reid
Lola M
LM
D000418:Albumins / Q000032:analysis; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D053539:Keratin-19 / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D019164:Liver, Artificial; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D023822:Tissue Engineering
D000418:Albumins; D018960:Hyaluronan Receptors; D020100:Hydrogels; D053539:Keratin-19; D006820:Hyaluronic Acid