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Experimental Biology and Medicine 230:860-864 (2005)
© 2005 Society for Experimental Biology and Medicine


ORIGINAL RESEARCH ARTICLE

Tissue Distribution of Fetal Liver Cells Following In Utero Transplantation in Mice

Mark A. Suckow1, Amy Zollman, Ivo Cornelissen, Michelle Casad, Julie Roahrig, Francis J. Castellino and Elliot D. Rosen

W.M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556

To whom requests for reprints should be addressed at 1 W.M. Keck Center for Transgene Research, 400 Freimann Life Center, University of Notre Dame, Notre Dame, IN 46556. E-mail: suckow.1{at}nd.edu

Transplantation of hepatic stem cells in utero has been advanced as a potential clinical approach to a variety of diseases, including deficiencies of coagulation factors. Although syngeneic transplantation has met with some success, consideration needs to be given to the potential for transplanted cells to colonize nontarget tissues. Liver cells were harvested from Rosa26 embyros at embryonic age 12.5 days postconception (pc) and transplanted into the peritoneal cavity of syngeneic recipients in utero. Tissues were harvested from tissue recipients at various time points ranging from 1 to 328 days pc, and tissues were stained for ß-galactosidase to identify the existence of cells derived from Rosa26 donors. ß-galactosidase-positive cells were found in the lung, liver, and brain as early as 20 days pc and through 328 days pc. Positive cells in these tissues existed as islands of cells that were morphologically similar to hepatocytes. In the spleen, individual ß-galactosidase-positive cells of both leukocytic and erythrocytic lineages were present, and suggest that hematopoietic cells were transferred to recipients along with hepatocytes. The lack of an inflammatory response to the ß-galactosidase-positive cells suggests that the donor cells were immunologically tolerated. In summary, the possibility that cells administered in utero may inadvertently colonize nontarget tissues suggests that clinical application of this method will need to be approached with diligence.

Key Words: hepatocytes • stem cells • transplantation • ß-galactosidase







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