Mature human hepatocytes from ex vivo differentiation of alginate-encapsulated hepatoblasts.
Alginate gel was used to provide encapsulation to support the growth and eventually the differentiation of hepatic progenitors cells derived from human fetal livers. The encapsulated cells aggregated into spheroids within a few days in culture and continued to grow for at least 4 weeks in a serum-free medium. The hepatic progenitor cells in the spheroids undergo differentiation, as indicated by the appearance of functions of mature hepatocytes such as the detoxification of ammonia, albumin secretion, expression of the adult cytochrome P450 isozyme CYP3A4 and enzymatic activity typical of CYP2C9. Along with the expression of mature hepatic markers, these progenitor cells lost features typical of immature liver cells such as epithelial cell adhesion molecule. In addition to the acquisition of mature biochemical functions, the spheroids also developed a bile ducts, suggesting that they had differentiated into tissues resembling those in an intact liver.
Cheng
Nancy
N
Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Wauthier
Eliane
E
Reid
L M
LM
D000418:Albumins / Q000378:metabolism; D000464:Alginates; D000641:Ammonia / Q000378:metabolism; D000943:Antigens, Differentiation / Q000096:biosynthesis; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001652:Bile Ducts / Q000166:cytology / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis; D020723:Glucuronic Acid; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006603:Hexuronic Acids; D006801:Humans; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors
D000418:Albumins; D000464:Alginates; D000943:Antigens, Differentiation; D006603:Hexuronic Acids; D000641:Ammonia; D020723:Glucuronic Acid; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human