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Maintainence of Primary Human Hepatocyte Function In Vitro by Extracellular Matrix Biologic Scaffolds

Sellaro, Tiffany Leigh (2008) Maintainence of Primary Human Hepatocyte Function In Vitro by Extracellular Matrix Biologic Scaffolds. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Liver disease is a leading cause of mortality in the United States. Tissue engineering and regenerative medicine (TE&RM) approaches to treating liver disease have the potential to provide temporary support with biohybrid artificial liver-assist devices or long-term therapy by replacing the diseased liver with functional tissue-engineered constructs that utilize a combination of cells, scaffolds and bioactive factors. A rate-limiting step for TE&RM technologies has been the loss of hepatocyte-specific functions in vitro after hepatocytes are isolated from their highly specialized in vivo microenvironment. The identification of a biologic substrate that can maintain a functional hepatocyte differentiation profile during in vitro culture would advance potential TE&RM therapeutic strategies. The present study is predicated upon the hypothesis that the substrate upon which hepatocytes are seeded is a critical determinant of cell phenotype and function. Biologic scaffolds composed of extracellular matrix (ECM) derived from mammalian organs have been used to maintain cell phenotype in vitro. Two studies were performed to evaluate the ability of ECM scaffolds to maintain primary human hepatocyte (PHH) phenotype in vitro. The first study evaluated the effect of ECM scaffolds derived from porcine liver (PLECM) and human liver (HLECM) upon maintainence of PHH specific functions in vitro. Cytochrome P450 activity and albumin secretion were used as indicators of hepatocyte functionality. No differences in hepatoycte-specific functions were measured when comparing PHH cultured with PLECM and HLECM. From a clinical perspective, the results are appealing because of the limited availability of human liver tissue compared to porcine liver tissue for the manufacture of ECM scaffolds.The second study cultured PHH between two layers of PLECM and compared with Matrigel double gel cultures and adsorbed type-1 collagen. Albumin secretion, hepatic transport activity and ammonia metabolism were used as markers of hepatocyte functionality. PHH cultured between two layers of porcine liver ECM had significantly higher levels of albumin secretion, hepatic transport activity, and ammonia metabolism compared to PHH cultured on collagen.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Sellaro, Tiffany
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBadylak, Stephen F.badylaks@upmc.eduSFB8
Committee MemberBeer-Stolz, Donnadstolz@pitt.eduDSTOLZ
Committee MemberPatzer, John F.patzer@pitt.eduPATZER
Committee MemberGerlach, Jorgejgerlach@pitt.eduJGERLACH
Committee MemberStrom, Stephenstrom@pitt.eduSTROM
Date: 8 September 2008
Date Type: Completion
Defense Date: 30 April 2008
Approval Date: 8 September 2008
Submission Date: 26 June 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: hepatic tissue engineering; human hepatoyctes; naturally-derived scaffolds
Other ID:, etd-06262008-105410
Date Deposited: 10 Nov 2011 19:48
Last Modified: 19 Dec 2016 14:36


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