scholarly journals PROPERTIES OF THE HEMOPOIETIC STEM CELL: CAN ITS BONE MARROW REPOPULATING ABILITY BE DISSOCIATED FROM IMMUNOLOGICAL COMPETENCE

1966 ◽  
Author(s):  
E.P. Cronkite
1977 ◽  
Vol 145 (6) ◽  
pp. 1567-1579 ◽  
Author(s):  
S Abramson ◽  
RG Miller ◽  
RA Phillips

The precise relationship between the stem cells for the lymphoid system and those for the blood-forming system is unclear. While it is generally assumed that the hemopoietic stem cell, the spleen colony-forming unit (CFU-S), is also the stem cell for the lymphoid system, there is little evidence for this hypothesis. To investigate the stem cells in these two systems, we irradiated bone marrow cells to induce unique chromosome aberrations in the stem cell population and injected them at limiting dilution into stem cell-deficient recipients. Several months (between 3 and 11) were allowed for the injected cells to repopulate the hemopoietic system. At that time, the bone marrow, spleen, and thymus were examined for a high frequency of cells having the same unique chromosome aberration. The presence of such markers shows that the marker was induced in a cell with extensive proliferative capacity, i.e., a stem cell. In addition, the splenic lymphocytes were stimulated with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) to search for unique chromosomes in dividing T and B cells, respectively. Finally, bone marrow cells were injected into secondary irradiated recipients to determine if the marker occurred in CFU-S and to determine whether or not the same tissue distributions of marked cells could be propogated by bone marrow cells in a second recipient. After examination of 28 primary recipients, it was possible to identify three unique patterns of stem cell regeneration. In one set of mice, a unique chromosome marker was observed in CFU-S and in PHA- and LPS-stimulated cultures. These mice provide direct evidence for a pluripotent stem cell in bone marrow. In addition, two restricted stem cells were identified by this analysis. In three recipients, abnormal karyotypes were found only in myeloid cells and not in B and T lymphocytes. These mice presumably received a marked stem cell restricted to differentiate only into myeloid progeny. In three other recipients, chromosome aberrations were found only in PHA-stimulated cells; CFU-S and cells from LPS cultures did not have cells with the unique chromosome. This pattern suggests that bone marrow contains cells committed to differentiation only into T lymphocytes. For each of the three types of stem cells, secondary recipients had the same cellular distribution of marked cells as the primary recipients. This observation provides further evidence that unique markers can be induced in both pluripotent and restricted stem cells.


Blood ◽  
2013 ◽  
Vol 122 (14) ◽  
pp. 2346-2357 ◽  
Author(s):  
Jau-Yi Li ◽  
Jonathan Adams ◽  
Laura M. Calvi ◽  
Timothy F. Lane ◽  
M. Neale Weitzmann ◽  
...  

Key Points Ovariectomy expands short-term hemopoietic stem and progenitor cells and improves engraftment and host survival after bone marrow transplantation. T cells are required for ovariectomy to expand hemopoietic stem and progenitor cells.


1978 ◽  
Vol 148 (5) ◽  
pp. 1351-1366 ◽  
Author(s):  
I Goldschneider ◽  
L K Gordon ◽  
R J Morris

Three approaches were used to demonstrate the presence of Thy-1 antigen on the surface of pluripotent hemopoietic stem cells in the rat. In the first, stem cells from fetal liver, neonatal spleen, and adult bone marrow were prevented from forming hemopoietic colonies in the spleens of irradiated recipients spleen (colony-forming unit assay) by incubation with antibodies to Thy-1 antigen. Highly specific rabbit heteroantiserum to purified rat brain Thy-1 antigen and mouse alloantisera to Thy-1.1-positive thymocytes were equally effective. This inhibition was neutralized by purified Thy-1 antigen. In a second series of experiments, Thy-1-positive and Thy-1-negative populations of nucleated bone marrow cells were separated by the FACS. All of the hemopoietic stem cell activity was recovered in the Thy-1-positive population. The stem cells were among the most strongly positive for Thy-1 antigen, being in the upper 25th percentile for relative fluorescence intensity. The relationships of Thy-1 antigen to the rat bone marrow lymphocyte antigen (BMLA) was shown in a third series of experiments. Rabbit anti-BMLA serum, which is raised against a null population of lymphocyte-like bone marrow cells, has been shown to have anti-stem cell activity. Here we demonstrate by double immunofluorescence, cocapping, and differential absorption studies that Thy-1 and BMLA are parts of the same molecule.


Blood ◽  
1980 ◽  
Vol 55 (6) ◽  
pp. 931-936 ◽  
Author(s):  
D Toksoz ◽  
TM Dexter ◽  
BI Lord ◽  
EG Wright ◽  
LG Lajtha

Abstract The isolation of a DNA synthesis inhibitor (NBME fraction IV) and stimulator (RBME fraction III) specific for the hemopoietic stem cell (CFU-s) from freshly isolated normal adult and regenerating murine bone marrow, respectively, has been well documented. We have utilized long- term liquid bone marrow cultures in a further analysis of the role of these factors in the regulation of CFU-s proliferation. Our results show that shortly after feeding, at a time when the cultured CFU-s are actively proliferating, high levels of the hemopoietic stem cell proliferation stimulator fraction III can be isolated from the culture medium. In contrast, the presence of essentially noncycling CFU-s found in cultures fed 8–10 days previously correlates with high levels of the hemopoietic stem cell inhibitor fraction IV. These results suggest that a certain balance between these factors determines CFU-s proliferation in the long-term cultures. In support of this, DNA synthesis in actively cycling CFU-s in the long-term cultures is inhibited for at least 3 days by the addition of excess NBME fraction IV (inhibitor). Furthermore, DNA synthesis in noncycling cultured CFU-s is stimulated for at least 5 days by the addition of RBME fraction III (stimulator).


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4990-4990
Author(s):  
Gabrielle L. Goldberg ◽  
Önder Alpdogan ◽  
Stephanie J. Muriglan ◽  
Maree Hammett ◽  
Morag K. Milton ◽  
...  

Abstract Age-related thymic atrophy plays a significant role in delayed immune reconstitution in older recipients after hemopoietic stem cell transplantations (HSCT). Sex steroid ablation has been shown to reverse thymic atrophy and previously we have shown that in syngeneic and allogeneic models of HSCT, sex steroid ablation enhances immune reconstitution. Donor-derived HSC numbers, as well as precursor T and B cells are increased in castrated mice following HSCT. These primary changes lead to an increase in both T and B cells in the periphery. The current study examined both the molecular mechanisms behind this enhanced reconstitution and the function of the lymphocytes produced. Bone marrow (BM) and thymic stromal cell (TSCs) populations were analysed using RT-PCR and were tested for the production of growth factors previously implicated in immune reconstitution. Functional studies including proliferation and cytotoxicity assays and intracellular cytokine production showed that on a per cell basis, there was no difference between the T cells from castrated and sham-castrated mice, following allogeneic HSCT. In vivo immune function was assessed using a delayed type hypersensitivity assay. Six weeks after HSCT the DTH response was enhanced in the castrated mice compared to sham-castrated controls. The combination of a) the increased number of donor-derived lymphocytes and b) intact T cell function, result in an overall increase in immune response (as determined by DTH) in castrated recipients of allogeneic HSCT. This enhanced function may be related to changes seen in growth factor production in the thymus and bone marrow.


Blood ◽  
1973 ◽  
Vol 42 (2) ◽  
pp. 195-208 ◽  
Author(s):  
K. A. Dicke ◽  
M. J. van Noord ◽  
B. Maat ◽  
U. W. Schaefer ◽  
D. W. van Bekkum

Abstract The colony-forming unit culture (CFU-C) in the thin-layer agar colony technique is considered to be representative for hemopoietic stem cells (HSC), according to our studies in mouse and monkey bone marrow. Using this in vitro assay as a guide, stem cell concentrates were prepared from monkey and human bone marrow by repeated density gradient centrifugation. The number of CFU-C could be enriched up to 70-100-fold. In such concentrated CFU-C suspensions, a cell, morphologically identical with the hemopoietic stem cell in the mouse (MSCLC, mouse stem cell-like cell) was frequently observed, using a May-Grünwald-Giemsa (MGG) staining method and electron microscope techniques. In MGG-stained preparations, the MSCLC superficially resembles the small lymphocyte; therefore, a staining method has been described, the polychrome procedure, by which both cell populations could be clearly distinguished. Since a fair correlation exists between the number of MSCLC and the number of CFU-C in a variety of primate hemopoietic suspensions, we concluded that the MSCLC might be a good candidate for being the HSC in monkeys and man.


Stem Cells ◽  
2005 ◽  
Vol 23 (4) ◽  
pp. 507-515 ◽  
Author(s):  
Magdaléna Sosnová ◽  
Monika Bradl ◽  
John V. Forrester

2008 ◽  
Vol 18 (9) ◽  
pp. 1884-1891 ◽  
Author(s):  
Jun Shen ◽  
James F. Griffith ◽  
Li-Na Cheng ◽  
Xiao-Hui Duan ◽  
Bi-Ling Liang ◽  
...  

2006 ◽  
Vol 82 (11) ◽  
pp. 1449-1456 ◽  
Author(s):  
Patrizia Ricci ◽  
Libuse Tauchmanova ◽  
Antonio Maria Risitano ◽  
Carlo Carella ◽  
Gherardo Mazziotti ◽  
...  

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