In utero transplanted human hepatocytes allow postnatal engraftment of human hepatocytes in pigs

James E. Fisher, Joseph B. Lillegard, Travis J. McKenzie, Brian R. Rodysill, Peter J. Wettstein, Scott Nyberg

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In utero cell transplantation (IUCT) can lead to the postnatal engraftment of human cells in the xenogeneic recipient. Most reports of IUCT have involved hematopoietic stem cells. It is unknown whether human hepatocytes used for IUCT in fetal pigs will lead to the engraftment of these same cells in the postnatal environment. In this study, fetal pigs received direct liver injections of 1 × 107 human hepatocytes in utero and were delivered by cesarean section at term. The piglets received a second direct liver injection of 5 × 107 human hepatocytes 1 week after birth. The serum was analyzed for human albumin 2, 4, and 6 weeks after engraftment. Piglet livers were harvested 6 weeks after transplantation and were examined by immunohistochemistry, polymerase chain reaction, and fluorescence in situ hybridization for human-specific sequences. Piglets undergoing IUCT with human hepatocytes that were postnatally engrafted with human hepatocytes showed significant levels of human albumin production in their serum at all postengraftment time points. Human albumin gene expression, the presence of human hepatocytes, and the presence of human beta-2 microglobulin were all confirmed 6 weeks after engraftment. IUCT in fetal pigs with human hepatocytes early in gestation allowed the engraftment of human hepatocytes, which remained viable and functional for weeks after transplantation. IUCT followed by postnatal engraftment may provide a future means for large-scale expansion of human hepatocytes in genetically engineered pigs. © 2013 AASLD.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalLiver Transplantation
Volume19
Issue number3
DOIs
StatePublished - Mar 2013

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Hepatocytes
Swine
Cell Transplantation
Albumins
Liver
Transplantation
beta 2-Microglobulin
Injections
Hematopoietic Stem Cells
Serum
Fluorescence In Situ Hybridization
Cesarean Section
Immunohistochemistry
Parturition
Gene Expression

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Hepatology

Cite this

Fisher, J. E., Lillegard, J. B., McKenzie, T. J., Rodysill, B. R., Wettstein, P. J., & Nyberg, S. (2013). In utero transplanted human hepatocytes allow postnatal engraftment of human hepatocytes in pigs. Liver Transplantation, 19(3), 328-335. https://doi.org/10.1002/lt.23598

In utero transplanted human hepatocytes allow postnatal engraftment of human hepatocytes in pigs. / Fisher, James E.; Lillegard, Joseph B.; McKenzie, Travis J.; Rodysill, Brian R.; Wettstein, Peter J.; Nyberg, Scott.

In: Liver Transplantation, Vol. 19, No. 3, 03.2013, p. 328-335.

Research output: Contribution to journalArticle

Fisher, JE, Lillegard, JB, McKenzie, TJ, Rodysill, BR, Wettstein, PJ & Nyberg, S 2013, 'In utero transplanted human hepatocytes allow postnatal engraftment of human hepatocytes in pigs', Liver Transplantation, vol. 19, no. 3, pp. 328-335. https://doi.org/10.1002/lt.23598
Fisher, James E. ; Lillegard, Joseph B. ; McKenzie, Travis J. ; Rodysill, Brian R. ; Wettstein, Peter J. ; Nyberg, Scott. / In utero transplanted human hepatocytes allow postnatal engraftment of human hepatocytes in pigs. In: Liver Transplantation. 2013 ; Vol. 19, No. 3. pp. 328-335.
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