Effects of transplantation on the primitive immunohematopoietic stem cell.

Harrison, David E.; Stone, M.; Astle, Clinton M.

doi:10.1084/jem.172.2.431

Cited by 153 publications

(105 citation statements)

References 16 publications

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“…However, whole BM cells from the same B6 and Trp53 null donors showed the opposite functional trend in recipient engraftment. Hematopoietic stem cells (HSCs) reside in fetal liver, cord blood and adult bone marrow (BM) in very low frequencies but perform a vital function of sustaining life-long production of all mature blood cells [1][2][3][4][5]. Various methods have been developed to enrich HSCs for functional studies as well as for clinical transplantation [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice

Chen

Ellison

Keyvanfar

et al. 2008

Experimental Hematology

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Objective-To test function of hematopoietic stem cells (HSCs) in vivo in C57BL/6 (B6) and Trp53-deficient (Trp53 null) mice by using two HSC enrichment schemes.Methods-Bone marrow (BM) Lin -CD41 -CD48 -CD150 + (SLAM, signaling lymphocyte activation molecules), Lin -CD41 -CD48 -CD150 -(SLAM -) and Lin -Sca1 + CD117 + (LSK) cells were defined by fluorescence activated cell staining (FACS). Cellular reactive oxygen species (ROS) level was also analyzed by FACS. Sorted SLAM, SLAM -and LSK cells were tested in vivo in the competitive repopulation (CR) and serial transplantation assays.Results-The SLAM cell fraction was 0.0078 ± 0.0010% and 0.0135 ± 0.0010% of total BM cells in B6 and Trp53 null mice, and was highly correlated (R 2 = 0.7116) with LSK cells. CD150 + BM cells also contained more ROS low cells than did CD150 -cells. B6 SLAM cells repopulated recipients much better than B6 SLAM-cells, showing high HSC enrichment. B6 SLAM cells also engrafted recipients better than Trp53 null SLAM cells in the CR and the follow-up serial transplantation assays. Similarly, LSK cells from B6 donors also had higher repopulating ability than those from Trp53 null donors. However, whole BM cells from the same B6 and Trp53 null donors showed the opposite functional trend in recipient engraftment. Hematopoietic stem cells (HSCs) reside in fetal liver, cord blood and adult bone marrow (BM) in very low frequencies but perform a vital function of sustaining life-long production of all mature blood cells [1][2][3][4][5]. Various methods have been developed to enrich HSCs for functional studies as well as for clinical transplantation [6][7][8][9][10]. HSCs lack the expression of cell surface molecules for lineage-specific mature cells, and are therefore Lin - [6,7,10]. In mouse models, HSCs usually express stem cell antigen 1 (Sca1 + ) and c-Kit (Kit + , CD117), a trans-membrane tyrosine kinase that serves as a receptor for stem cell factor [10][11][12]. These findings led to the establishment of Lin -Sca1 + Kit + (LSK) as a standard marker set for HSCs, although other Conclusion-Both

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Section: Introductionmentioning

confidence: 99%

Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice

Chen

Ellison

Keyvanfar

et al. 2008

Experimental Hematology

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“…To observe the protein bands, an enzymatic stain specific for Gpi was mixed in hot agar and was layered over the gel surface. 13 The quality of platelet preps was monitored by counting contaminating leukocytes and erythrocytes on platelet preps stained with May-Grunwald Giemsa. Levels of contamination were consistently less than 1%.…”

Section: Platelet Cell Harvest and Analysismentioning

confidence: 99%

The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells

Slayton

Georgelas

Pierce

et al. 2002

Blood

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The stem cell pool can be fractionated by using the mitochondrial dye, rhodamine-123, into Rho low hematopoietic stem cells and Rho high progenitors. Rho low stem cells permanently engraft all lineages, whereas Rho high progenitors transiently produce erythrocytes, without substantial platelet or granulocyte production. We hypothesized that the inability of the Rho high cells to produce platelets in vivo was due to the fact that these cells preferentially engraft in the spleen and lack marrow engraftment. Initially, we demonstrated that Rho high progenitors produced more megakaryocytes in vitro than Rho low stem cells did. To study the activity of the Rho low and Rho high subsets in vivo, we used mice allelic at the hemoglobin and glucose phosphate isomerase loci to track donor-derived erythropoiesis and thrombopoiesis. Rho low stem cells contributed to robust and long-term erythroid and platelet engraftment, whereas Rho high progenitors contributed only to transient erythroid engraftment and produced very low numbers of platelets in vivo. Donorderived megakaryopoiesis occurred at higher densities in the spleen than in the bone marrow in animals receiving Rho low stem cells and peaked around day 28. Blockade of splenic engraftment using pertussis toxin did not affect the peak of splenic megakaryopoiesis, supporting the hypothesis that these megakaryocytes were derived from progenitors that originated in the bone marrow. These data emphasize that in vitro behavior of hematopoietic progenitor cell subsets does not always predict their behavior following transplantation. This study supports a major role for the spleen in thrombopoi IntroductionMurine hematopoietic stem cells have been shown to reside within a population of cells that do not express lineage-specific markers (Lin neg ) and express the antigens Sca-1, c-kit, and Thy-1.1. Cells of this phenotype comprise the stem cell pool in certain strains of mice. 1,2 Rhodamine-123 (Rho) is a mitochondrial dye that stains cells based on their state of activation in which the more metabolically active cells tend to fluoresce brightly and quiescent cells dimly. 3 Rho has been used to subfractionate the stem cell pool into quiescent and metabolically active subsets. The Rho low subset is highly enriched for hematopoietic stem cells, to the degree that as few as 4 of these cells can reconstitute a mouse for the lifetime of the animal. Observations of the behavior of these stem cells have led to the model of the 2-tiered stem-cell pool. 4 According to this model, the Rho low cells make rare contributions to the peripheral compartment, but are mobilized in response to physiologic needs, and represent most of the transplantable stem cells. In contrast, Rho high cells have a high rate of cell division and, thus, make frequent contributions to the peripheral compartment under normal conditions. However, Rho high cells perform poorly in transplantation experiments, producing mainly erythrocytes and contributing little to platelet or granulocyte recovery. 5,6 All previous stu...

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“…The frequency of human and murine hematopoietic stem cells has been estimated to be 1/10 4 -10 5 bone marrow cells (Harrison et al, 1989;Sutherland et al, 1989;Harrison, 1993;Szilvassy and Hoffman, 1995;Bhatia et al, 1998;Abkowitz et al, 2002). The rarity of this population presented considerable impediments to isolation until recently.…”

Section: Methods Of Identifying Hematopoietic Stem and Progenitor Cellsmentioning

confidence: 99%

Blood cell progenitors: Insights into the properties of stem cells

Yöder

2003

Anat. Rec.

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Hematopoiesis is a dynamic process in which eight lineages of mature blood cells are derived from a common stem cell. Great progress has been made in identifying the functionally disparate progenitors that emerge from the stem cell and in elucidating the molecules required for their growth and survival. Further work will be required to understand the molecular mechanisms that regulate commitment of stem and progenitor cells to each stage of progenitor cell development and ultimately into the mature blood cells. Anat Rec Part A 276A: 66 -74, 2004.

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Effects of transplantation on the primitive immunohematopoietic stem cell.

Cited by 153 publications

References 16 publications

Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice

Enrichment of hematopoietic stem cells with SLAM and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice

The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells

Blood cell progenitors: Insights into the properties of stem cells

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