The feasibility of the Alb-uPA/SCID/Bg chimeric mouse as a model for Hepatitis C Virus (HCV)
infection was assessed experimentally by (1) the infection and treatment with another
hepatotropic virus, Hepatitis B Virus (HBV) and (2) the infection of the model with HCV and the
subsequent treatment of that infection with a pro-apoptotic factor (BID) targeted to infected
hepatocytes. In the former, the infected mouse responded favorably, and in the manner of human
patients, to a standard imunoglobulin therapy. In the latter, HCV-infected hepatocytes were
successfully targeted for cell death, with repeated doses of Adenovirus-delivered BID being the
most effective at inhibiting virus spread. Efficacy and toxic side-effects of BID treatment could
be reconciled by modulating the timing between doses, the most effective tested being three doses
of BID at 7-day intervals. Analyses of chimeric model production were undertaken to improve
the quality of human hepatocyte engraftment (typically only 25-35% of mice receiving grafts are
currently used experimentally). Minor variations in success rates were experienced with respect
to donor age or health status, or the age of recipient mice within an operational window of 5 to 13
days from birth. The greatest obstacle to useful engraftment (aside from technical challenges)
was deemed to be the genetic/cellular integrity of the recipient mouse. This conclusion was
based on variable engraftment success with ‘healthy’ donor cell preparations and a consideration
of variability in immune deficiency arising in mice within a SCID/Bg mouse colony. / Experimental Surgery
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/765 |
| Date | 11 1900 |
| Creators | Hsi Dickie, Belinda |
| Contributors | Kneteman, Norman M (Surgery), Elliot, John F (Medical Microbiology and Immunology), Tyrell, D. Lorne (Medical Microbiology and Immunology), Churchill, Thomas A (Surgery), Humar, Atul (Medicine), Kay, Mark A (Department of Pediatrics and Genetics, Stanford University) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 2649838 bytes, application/pdf |
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