Autor: |
Lemoli, Roberto M., Bertolini, Francesco, Petrucci, Maria T., Gregorj, Chiara, Ricciardi, Maria R., Fogli, Miram, Curti, Antonio, Rabascio, Cristina, Pandolfi, Simona, Ferrari, Sergio, Fo, Robin, Baccarani, Michele, Tafuri, Agostino |
Předmět: |
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Zdroj: |
British Journal of Haematology; Nov2003, Vol. 123 Issue 4, p720, 10p |
Abstrakt: |
We assessed the functional properties and the kinetic status in vitro, and the engraftment potential in vivo of human haematopoietic stem cells according to the expression of CD34 antigen. Lin−CD34− and Lin−CD34+ cells were isolated from granulocyte colony-stimulating factor-primed peripheral blood (PB) cells of healthy donors. The CD34− cell fraction did not contain either clonogenic cells in semisolid culture or long-term culture initiating cells (LTC-IC). However, stroma-dependent liquid cultures and cytokines induced CD34 expression on a minority of stem cells, acquisition of clonogenic capacity and generation of LTC-IC. Significantly higher percentages of quiescent G0 cells and lower percentages of cycling G1 cells were found in Lin−CD34− cells when compared with Lin−CD34+ cells. Kinetic quiescence of Lin−CD34− cells was associated with a significantly higher expression of the negative regulators of the cell cycle, p27Kip1 and p21cip1/waf1. Cytokine-mediated induction of CD34, in vitro, resulted in cycling of stem cells and downregulation of p27. There was a higher rate of human long-term engraftment in immunocompromised non-obese diabetic (NOD)/recombination activating gene 1null and NOD/severe combined immunodeficient-β2microglobulinnull mice injected with CD34+ cells. Thus, our study indicated that CD34 expression on human PB stem cells was associated with haematopoietic activity, cell-cycle recruitment and downregulation of p27Kip1 in vitro and higher engraftment capacity in vivo. [ABSTRACT FROM AUTHOR] |
Databáze: |
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