Human and rhesus macaque hematopoietic stem cells cannot be purified based only on SLAM family markers
ABSTRACT 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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- "Human and murine bone marrow cells, however, display different SRR molecules, and human long-term HSC have been reported to be CD150 negative . Therefore CD150 in humans may not be a useful marker for improving purification of long-term HSC . 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 . "
ABSTRACT: Stem cells are able to generate both cells that differentiate and cells that remain undifferentiated but potentially have the same developmental program. The prolonged duration of the protective immune memory for infectious diseases such as polio, small pox, and measles, suggested that memory T cells may have stem cell properties. Understanding the molecular basis for the life-long persistence of memory T cells may be useful to project targeted therapies for immune deficiencies and infectious diseases and to formulate vaccines. In the last decade evidence from different laboratories shows that memory T cells may share self-renewal pathways with bone marrow hematopoietic stem cells. In stem cells the intrinsic self-renewal activity, which depends on gene expression, is known to be modulated by extrinsic signals from the environment that may be tissue specific. These extrinsic signals for stemness of memory T cells include cytokines such as IL-7 and IL-15 and there are other cytokine signals for maintaining the cytokine signature (TH1, TH2, etc.) of memory T cells. Intrinsic and extrinsic pathways that might be common to bone marrow hematopoietic stem cells and memory T lymphocytes are discussed and related to self-renewal functions.Cytokine & growth factor reviews 10/2013; 24(6). DOI:10.1016/j.cytogfr.2013.10.002 · 6.54 Impact Factor
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ABSTRACT: The understanding of the hierarchical organization of the human hematopoietic system is of major biologic and clinical significance. The validity of the conventional model in which hematopoiesis is solely maintained by a pool of multipotent long-term hematopoietic stem cells (LT-HSCs) has been recently challenged by several mouse studies. These new data point to the existence of a heterogeneous stem cell population that consists of distinct subsets of LT-HSCs, which include stem cells biased toward lineage-specific differentiation programs. This review attempts to discuss the balanced versus biased patterns of lineage output of human LT-HSCs gathered in 3 different gene therapy trials on the basis of vector integration site analysis by deep sequencing. The distribution of integration sites observed tends to support the validity of the revised model.Blood 02/2011; 117(17):4420-4. DOI:10.1182/blood-2010-09-255679 · 10.43 Impact Factor
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ABSTRACT: Transient lymphopenia is a hallmark of measles virus (MV)-induced immunosuppression. To address to what extent replenishment of the peripheral lymphocyte compartment from bone marrow (BM) progenitor/stem cells might be affected, we analyzed the interaction of wild-type MV with hematopoietic stem and progenitor cells (HS/PCs) and stroma cells in vitro. Infection of human CD34(+) HS/PCs or stroma cells with wild-type MV is highly inefficient yet noncytolytic. It occurs independently of CD150 in stroma cells but also in HS/PCs, where infection is established in CD34(+) CD150(-) and CD34(+) CD150(+) (in humans representing HS/PC oligopotent precursors) subsets. Stroma cells and HS/PCs can mutually transmit MV and may thereby create a possible niche for continuous viral exchange in the BM. Infected lymphocytes homing to this compartment may serve as sources for HS/PC or stroma cell infection, as reflected by highly efficient transmission of MV from both populations in cocultures with MV-infected B or T cells. Though MV exposure does not detectably affect the viability, expansion, and colony-forming activity of either CD150(+) or CD150(-) HS/PCs in vitro, it efficiently interferes with short- but not long-term hematopoietic reconstitution in NOD/SCID mice. Altogether, these findings support the hypothesis that MV accession of the BM compartment by infected lymphocytes may contribute to peripheral blood mononuclear cell lymphopenia at the level of BM suppression.Journal of Virology 05/2011; 85(15):7710-8. DOI:10.1128/JVI.00532-11 · 4.65 Impact Factor