Human and rhesus macaque hematopoietic stem cells cannot be purified based only on SLAM family markers

National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Blood (Impact Factor: 10.45). 02/2011; 117(5):1550-4. DOI: 10.1182/blood-2009-03-212803
Source: PubMed


Various combinations of antibodies directed to cell surface markers have been used to isolate human and rhesus macaque hematopoietic stem cells (HSCs). These protocols result in poor enrichment or require multiple complex steps. Recently, a simple phenotype for HSCs based on cell surface markers from the signaling lymphocyte activation molecule (SLAM) family of receptors has been reported in the mouse. We examined the possibility of using the SLAM markers to facilitate the isolation of highly enriched populations of HSCs in humans and rhesus macaques. We isolated SLAM (CD150(+)CD48(-)) and non-SLAM (not CD150(+)CD48(-)) cells from human umbilical cord blood CD34(+) cells as well as from human and rhesus macaque mobilized peripheral blood CD34(+) cells and compared their ability to form colonies in vitro and reconstitute immune-deficient (nonobese diabetic/severe combined immunodeficiency/interleukin-2 γc receptor(null), NSG) mice. We found that the CD34(+) SLAM population contributed equally or less to colony formation in vitro and to long-term reconstitution in NSG mice compared with the CD34(+) non-SLAM population. Thus, SLAM family markers do not permit the same degree of HSC enrichment in humans and rhesus macaques as in mice.

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    • "In fact, the only hematopoietic cell populations in mice that distinctly lack CD48 expression in mice are neutrophils and a subset of long-term hematopoietic stem cells (LT-HSCs)[59,60]. However, in humans CD48 is also found on neutrophils and other HSC types[61,62]Monocytes and lymphocytes have elevated CD48 expression in patients with viral and bacterial infections[61]. Patients with EBV infection or arthritis exhibit elevated levels of soluble CD48 in the serum[52]. "
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    • "Human and murine bone marrow cells, however, display different SRR molecules, and human long-term HSC have been reported to be CD150 negative [25]. Therefore CD150 in humans may not be a useful marker for improving purification of long-term HSC [26]. Finally, it has been recently found that human HSC coexpressing Thy-1 and the adhesion molecule a6 integrin (CD49f) which is not expressed by multipotent progenitors, were the most effective in long-term engraftment, and a single cell of this type could give rise to all hematopoietic lineages in vivo [27]. "
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