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Induction of Hepatocyte Differentiation by the Extracellular Matrix and an RGD-Containing Synthetic Peptide

Published online by Cambridge University Press:  15 February 2011

David J. Mooney ,
Robert Langer ,
Linda K. Hansen ,
Joseph P. Vacanti  and
Donald E. Ingber
David J. Mooney
Affiliation:
Dept. Chemical Engineering, MIT, 77 Massachusetts Ave., Cambridge, MA 02139
Robert Langer
Affiliation:
Dept. Chemical Engineering, MIT, 77 Massachusetts Ave., Cambridge, MA 02139
Linda K. Hansen
Affiliation:
Dept. of Surgery, Children's Hospital, 300 Longwood Ave., Boston, MA 02115
Joseph P. Vacanti
Affiliation:
Dept. of Surgery, Children's Hospital, 300 Longwood Ave., Boston, MA 02115
Donald E. Ingber
Affiliation:
Dept. of Surgery, Children's Hospital, 300 Longwood Ave., Boston, MA 02115
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Abstract

To design novel biomaterials for hepatocyte transplantation it will be necessary to determine whether specific extracellular matrix (ECM) molecule(s) or the adhesive interactions between the surface and hepatocytes are responsible for regulation of hepatocyte function. Purified ECM molecules (laminin, fibronectin, types I and IV collagen) and a synthetic peptide containing the arginine-glycine-aspartate (RGD) cell-binding sequence were precoated at defined densities to non-adhesive polystyrene dishes. Hepatocytes cultured on dishes coated with a low density of ECM molecules (1 ng/cm2) maintained a round morphology, and high liver-specific protein secretion rates. In contrast, culturing hepatocytes on increasing ECM densities (50–1000 ng/cm2) resulted in extensive cell spreading, a loss of liver-specific protein secretion, and cell growth. Hepatocytes cultured on dishes coated with the RGD-containing peptide did not spread even on a high density of the peptide (10,000 ng/cm2), and albumin secretion remained high for hepatocytes cultured on all peptide densities (1–10,000 ng/cm2). These results suggest that a variety of ECM molecules and synthetic peptides are capable of inducing hepatocyte differentiation in vitro, and these effects depend on their ability to promote cell spreading.

Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 252: Symposium T – Tissue-Inducing Biomaterials , 1991 , 199
Copyright
Copyright © Materials Research Society 1992

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References

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