Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes.

作者: Markus Grompe , Milton Finegold , Muhsen Al-Dhalimy , Ken Overturf , Ching Nan Ou

DOI:

关键词: TransplantationStem cellSerial TransplantationHaematopoiesisPathologyCell biologyLiver Stem CellLiver cytologyLiver regenerationBiologyFumarylacetoacetate hydrolase

摘要: Previous work has shown that adult mouse hepatocytes can divide at least 18 times in vivo. To test whether this represents the upper limit of their regenerative capacity, we performed serial transplantation fumarylacetoacetate hydrolase deficiency murine model liver repopulation. Hepatocytes from donors were serially transplanted limiting numbers six and resulted complete repopulation during each cycle. This corresponds to a minimal number 69 cell doublings or 7.3 x 10(20)-fold expansion. No evidence for abnormal function altered hepatic architecture was found repopulated animals. We conclude fraction have growth potential similar hematopoietic stem cells.

参考文章(31)
J. W. Grisham, G. J. Smith, W. B. Coleman, A. E. Wennerberg, Regulation of the differentiation of diploid and some aneuploid rat liver epithelial (stemlike) cells by the hepatic microenvironment American Journal of Pathology. ,vol. 142, pp. 1373- 1382 ,(1993)
A. L. Horwich, Inherited Hepatic Enzyme Defects as Candidates for Liver-Directed Gene Therapy Current Topics in Microbiology and Immunology. ,vol. 168, pp. 185- 200 ,(1991) , 10.1007/978-3-642-76015-0_9
R M Tanguay, C Laberge, M Plante, J L Duband, A Lescault, F Lettre, J P Valet, Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I). American Journal of Human Genetics. ,vol. 47, pp. 308- 316 ,(1990)
Snorri S. Thorgeirsson, Hepatic stem cells in liver regeneration. The FASEB Journal. ,vol. 10, pp. 1249- 1256 ,(1996) , 10.1096/FASEBJ.10.11.8836038
M Grompe, M al-Dhalimy, M Finegold, C N Ou, T Burlingame, N G Kennaway, P Soriano, Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice. Genes & Development. ,vol. 7, pp. 2298- 2307 ,(1993) , 10.1101/GAD.7.12A.2298
G Kelsey, S Ruppert, F Beermann, C Grund, R M Tanguay, G Schutz, Rescue of mice homozygous for lethal albino deletions: Implications for an animal model for the human liver disease tyrosinemia type 1 Genes & Development. ,vol. 7, pp. 2285- 2297 ,(1993) , 10.1101/GAD.7.12A.2285
Ken Overturf, Muhsen Al-Dhalimy, Robert Tanguay, Mark Brantly, Ching-Nan Ou, Milton Finegold, Markus Grompe, Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I Nature Genetics. ,vol. 12, pp. 266- 273 ,(1996) , 10.1038/NG0396-266
Eric P. Sandgren, Richard D. Palmiter, Janice L. Heckel, Cynthia C. Daugherty, Ralph L. Brinster, Jay L. Degen, Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene. Cell. ,vol. 66, pp. 245- 256 ,(1991) , 10.1016/0092-8674(91)90615-6
Grant R. MacGregor, Anne E. Mogg, Julian F. Burke, C. Thomas Caskey, Histochemical staining of clonal mammalian cell lines expressing E. coli beta galactosidase indicates heterogeneous expression of the bacterial gene. Somatic Cell and Molecular Genetics. ,vol. 13, pp. 253- 265 ,(1987) , 10.1007/BF01535207
J. A. Rhim, E. P. Sandgren, R. D. Palmiter, R. L. Brinster, Complete reconstitution of mouse liver with xenogeneic hepatocytes Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 4942- 4946 ,(1995) , 10.1073/PNAS.92.11.4942