Increased differentiation properties in two- and three-dimensional coculture of hepatocytes and liver epithelial cells by a novel quantitative functional liver assay

Hepatic stem cells in adult rats are activated by chemical injury to the liver, causing hepatic progenitor cells to proliferate, integrate into the hepatic plates, and differentiate into hepatocytes. In an attempt to model this process in vitro, we established and quantitatively assayed the differentiation properties of a strain of rat liver epithelial cells (LEC), lig8, grown in coculture with mature liver cells in a three dimensional, perfused microreactor optimized for hepatocyte culture. Lig8 was derived by suppression of the asymmetric growth kinetics that may be indicative of stem cells, and Lig8 progeny can be induced to exhibit several hepatocyte-specific differentiation properties in vitro; however, Lig8 full hepatocyte functional differentiation in culture has not yet been achieved. We hypothesized that more extensive differentiation properties may be observed in vitro if the Lig8 cells are cultured in an engineered analog of the 3D tissue environment that influences progenitor cell differentiation in vivo. We also assayed the differentiation properties of the hepatocytes in coculture. Previous studies have shown an increase in the differentiation of hepatocytes in 2D hepatocyte-LEC cocultures; we wished to determine if the benefit of coculture also occurs in the 3D microreactor.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Moritz, Joseph M. (Joseph Michael)

Advisor dc:contributor.advisor

• Linda G. Griffith and James L. Sherley.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/39352
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/39352

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39352