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

First Author  Uchida N Year  2002
Journal  Exp Hematol Volume  30
Issue  8 Pages  862-9
PubMed ID  12160837 Mgi Jnum  J:119430
Mgi Id  MGI:3702211 Doi  10.1016/s0301-472x(02)00879-2
Citation  Uchida N, et al. (2002) Liver and marrow of adult mdr-1a/1b(-/-) mice show normal generation, function, and multi-tissue trafficking of primitive hematopoietic cells. Exp Hematol 30(8):862-9
abstractText  OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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