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Modulation of hepatic tissue functio...

Allen, Jared W.

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Modulation of hepatic tissue function by oxygen in vitro.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Modulation of hepatic tissue function by oxygen in vitro./
Author:	Allen, Jared W.
Description:	152 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1968.
Contained By:	Dissertation Abstracts International65-04B.
Subject:	Engineering, Biomedical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3129953
ISBN:	0496772082

Modulation of hepatic tissue function by oxygen in vitro.
Allen, Jared W.

Modulation of hepatic tissue function by oxygen in vitro. - 152 p.

Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1968.

Thesis (Ph.D.)--University of California, San Diego, 2004.

Development of in vitro models of the liver that recapitulate the microenvironmental cues of hepatocytes in vivo is of great value to understanding normal liver physiology and pathology. Generally overlooked in current in vitro systems, oxygen can be an important modulator of cellular functions. In particular, cellular responses to oxygen availability, both for metabolism and signaling, play a critical role liver metabolism, biotransformation, stress response, and toxicity.

ISBN: 0496772082Subjects--Topical Terms:

1017684
Engineering, Biomedical.

Modulation of hepatic tissue function by oxygen in vitro.
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035 $a (UnM)AAI3129953
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040 $a UnM $c UnM
100 1 $a Allen, Jared W. $3 1939193
245 1 0 $a Modulation of hepatic tissue function by oxygen in vitro.
300 $a 152 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1968.
500 $a Chair: Sangeeta N. Bhatia.
502 $a Thesis (Ph.D.)--University of California, San Diego, 2004.
520 $a Development of in vitro models of the liver that recapitulate the microenvironmental cues of hepatocytes in vivo is of great value to understanding normal liver physiology and pathology. Generally overlooked in current in vitro systems, oxygen can be an important modulator of cellular functions. In particular, cellular responses to oxygen availability, both for metabolism and signaling, play a critical role liver metabolism, biotransformation, stress response, and toxicity.
520 $a As a novel perfusion model of the liver, a small-scale bioreactor was developed that allows physiologic oxygen gradients to be imposed on hepatocyte cultures recapitulating the in vivo microenvironment. Following modeling and validation of oxygen gradients in vitro, we examined the establishment of heterogeneous hepatocyte populations in terms of metabolism, detoxification, and toxicity. Perused hepatocyte cultures and co-cultures of hepatocytes and fibroblasts displayed regional expression patterns of metabolic and cytochrome P450 enzymes that parallel distributions in the zonated liver. Furthermore, perfusion of acetaminophen, a well-characterized liver toxin, resulted in regional toxicity that models pericentral necrosis seen in vivo.
520 $a Interested in the mechanisms of cellular oxygen sensing, we examined specific pathways by which hepatocytes adapt to low oxygen environments. Primary murine hepatocytes nullizygous for HIF-1alpha, a key regulator of hypoxic response, were characterized in long-term collagen sandwich culture. Genome-wide analysis of gene expression by microarray technology was implemented to identify the constellation of genes differentially expressed under hypoxia and regulated by HIF-1alpha. Validation of several hypoxia-responsive genes indicated a potential role for HIF-1alpha in metabolic adaptation, growth factor secretion, and hepatocyte priming. Further studies to investigate the interaction of HIF-1alpha and dioxin signaling pathways showed that HIF-1alpha is not a negative regulator of transcription in the dioxin pathway but may indirectly alter biotransformation capacity in hepatocytes.
520 $a Collectively, these studies establish biomimetic culture models that clarify the role of oxygen in liver function and highlight its potential applications in hepatic tissue engineering.
590 $a School code: 0033.
650 4 $a Engineering, Biomedical. $3 1017684
650 4 $a Biology, Cell. $3 1017686
650 4 $a Biology, Animal Physiology. $3 1017835
690 $a 0541
690 $a 0379
690 $a 0433
710 2 0 $a University of California, San Diego. $3 1018093
773 0 $t Dissertation Abstracts International $g 65-04B.
790 1 0 $a Bhatia, Sangeeta N., $e advisor
790 $a 0033
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3129953