Hypoxia leads to necrotic hepatocyte death
dc.contributor.author | Smith, Molly K. | en_US |
dc.contributor.author | Mooney, David J. | en_US |
dc.date.accessioned | 2007-09-20T18:20:45Z | |
dc.date.available | 2008-04-03T18:52:43Z | en_US |
dc.date.issued | 2007-03-01 | en_US |
dc.identifier.citation | Smith, Molly K.; Mooney, David J. (3)."Hypoxia leads to necrotic hepatocyte death." Journal of Biomedical Materials Research Part A 80A: 520-529. <http://hdl.handle.net/2027.42/55977> | en_US |
dc.identifier.issn | 1549-3296 | en_US |
dc.identifier.issn | 1552-4965 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/55977 | |
dc.description.abstract | Hepatocyte transplantation is being investigated as a therapy for liver disease; however, its success has been limited by rapid death of the cells following transplantation. This study was dedicated to elucidating the mode of death responsible for loss of transplanted hepatocytes in order to guide future strategies for promoting their survival. Using a tissue engineering model, it was found that the environment within polymer scaffolds containing transplanted cells was hypoxic after 5 days in vivo , with (90 ± 3)% of hepatocytes existing at pO 2 < 10 mmHg. The primary mode of hepatocyte death in response to hypoxic conditions of 0 or 2 vol % oxygen was then determined in vitro . Several assays for features of apoptosis and necrosis demonstrated that hepatocytes cultured in an anoxic environment died via necrosis, while culture at 2% oxygen inhibited proliferation. These results suggest it will not be possible to prevent hepatocyte death by interfering with the apoptotic process, and hypoxic conditions in the transplants must instead be addressed. The finding that the environment within cell transplantation scaffolds is hypoxic is likely applicable to many cell-based therapies, and a similar analysis of the primary mode of death for other cell types in response to hypoxia may be valuable in guiding future strategies for their transplantation. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007 | en_US |
dc.format.extent | 465772 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Polymer and Materials Science | en_US |
dc.title | Hypoxia leads to necrotic hepatocyte death | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biomedical Engineering | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109 | en_US |
dc.contributor.affiliationother | Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138 ; 325 Pierce Hall, 29 Oxford Street, Cambridge, MA 02138, USA | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/55977/1/30930_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/jbm.a.30930 | en_US |
dc.identifier.source | Journal of Biomedical Materials Research Part A | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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