期刊
TISSUE ENGINEERING PART A
卷 16, 期 9, 页码 2731-2741出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2009.0695
关键词
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资金
- National Institutes of Health [NIDDK-1R21DK077802]
- National Science Foundation [DMR-090750]
- Thomas F. and Kate Miller Jeffress Foundation
- Institute for Critical Technology and Applied Sciences
- Virginia Polytechnic Institute and State University
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK077802] Funding Source: NIH RePORTER
- Direct For Mathematical & Physical Scien [0907590] Funding Source: National Science Foundation
Interactions between hepatocytes and liver sinusoidal endothelial cells (LSECs) are essential for the development and maintenance of hepatic phenotypic functions. We report the assembly of three-dimensional liver sinusoidal mimics comprised of primary rat hepatocytes, LSECs, and an intermediate chitosan-hyaluronic acid polyelectrolyte multilayer (PEM). The height of the PEMs ranged from 30 to 55nm and exhibited a shear modulus of similar to 100 kPa. Hepatocyte-PEM cellular constructs exhibited stable urea and albumin production over a 7-day period, and these values were either higher or similar to cells cultured in a collagen sandwich. This is of significance because the thickness of a collagen gel is similar to 1000-fold higher than the height of the chitosan-hyaluronic acid PEM. In the hepatocyte-PEM-LSEC liver-mimetic cellular constructs, LSEC phenotype was maintained, and these cultures exhibited stable urea and albumin production. CYP1A1/2 activity measured over a 7-day period was significantly higher in the hepatocyte-PEM-LSEC constructs than in collagen sandwich cultures. A 16-fold increase in CYP1A1/2 activity was observed for hepatocyte-PEM-10,000 LSEC samples, thereby suggesting that interactions between hepatocytes and LSECs are critical in enhancing the detoxification capability in hepatic cultures in vitro.
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