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Exp Hematol. 2002 Aug;30(8):862-9.

Liver and marrow of adult mdr-1a/1b(-/-) mice show normal generation, function, and multi-tissue trafficking of primitive hematopoietic cells.

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  • 1Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medical Genetics, Medicine and Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.



Several lines of evidence suggest that expression of two ABC transporters (Abcg2/Bcrp1 and mdr-1a/b) and the related abilities to efflux Hoechst 33342 (Hst) and Rhodamine-123 (Rho) are features of primitive hematopoietic cells in adult bone marrow. Here we sought to determine the phenotypic and hematopoietic properties of the Hst-effluxing "side" population (SP) cells present in the liver of adult normal mice and whether these might be altered in mdr-1a/1b(-)(/-) mice.


Single-cell suspensions of liver (and sometimes bone marrow) were stained with Hst, separated into SP and non-SP fractions, and analyzed for hematopoietic cell-surface marker expression and functional activity in standard in vitro and in vivo (transplantation) assays.


SP cells constituted approximately 1-2% of adult liver cell suspensions and were phenotypically and functionally heterogeneous, even within the approximately 20-25% that expressed CD45. The latter included some lineage marker-positive (lin(+)) cells, less than 15% of all in vitro hematopoietic colony-forming cells in the adult liver and more than 90% of cells identified as long-term culture-initiating cells or in vivo repopulating cells. Interestingly, primary mice reconstituted for greater than or equal to 1 year with adult liver SP cells contained derivative primitive hematopoietic cells in their livers. No differences were seen between +/+ and mdr-1a/1b(-)(/-) mice except for a loss of Rho efflux ability by lin(-)mdr-1a/1b(-)(/-) SP cells.


Adult murine liver contains a spectrum of hematopoietic cells that are phenotypically and functionally similar to those in the marrow and their generation and properties appear unaffected by a lack of mdr-1a/1b.

[PubMed - indexed for MEDLINE]
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