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A model to quantitate cell transplant function after liver-specific injury

Authors
Journal
Journal of Surgical Research
0022-4804
Publisher
Elsevier
Publication Date
Volume
114
Issue
2
Identifiers
DOI: 10.1016/j.jss.2003.08.115
Keywords
  • Abstract
Disciplines
  • Medicine

Abstract

Abstract Introduction: As the study of hepatic cytotherapeutics requires 1) selective pressure to improve engraftment of transplanted cells, and 2) a method to assess the hepatocyte-specific function of transplanted cells, we created a model to quantitate the functional engraftment of transplanted cells following liver-specific injury. Methods: Transgenic mice expressing human alpha-1 antitrypsin (hAAT) linked to the albumin promoter were used for donor cells. Liver injury was mediated through adenovirus transfection of urokinase-type tissue plasminogen activator (uPA). After uPA administration, 10 x 6 hAAT hepatocytes were injected into juvenile SCID mice. Control animals were uninjured. Recipients were bled serially after transplantation and the serum samples assessed for hAAT via ELISA. Results: Injection of uPA increased transaminase levels transiently, confirming hepatocyte injury. Uninjured SCID mice expressed 250 nanograms/mL of hAAT after injection of 10 x 6 hepatocytes. Mice receiving uPA prior to hepatocyte administration expressed 25 micrograms/mL of hAAT. Conclusions: uPA administration results in a 100-fold increase in transplanted hepatocyte engraftment and function. This model offers a method to confer positive selection for liver engraftment and yields a quantifiable increase in the hepatocyte-specific function of transplanted cells. This data establishes a basis to compare the kinetics of engraftment and function of cellular transplants from various sources after acute liver injury.

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