Haemopoietic stem cells: their heterogeneity and regulation

Graham, Gerard J.; Wright, Esmond

doi:10.1046/j.1365-2613.1997.270361.x

Cited by 40 publications

(15 citation statements)

References 117 publications

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“…In this transplantation model, cells derived from the small number of transplanted donor stem cells will have reestablished a stem cell compartment and reconstituted the hemopoietic system (20), and it is improbable that any cells examined cytogenetically were those present in the original irradiated population. Whereas some transmitted delayed effect of irradiation might explain the chromosomal instability and deficit in contribution to repopulation in the progeny of irradiated stem cells, chromosomal instability in the progeny of unirradiated 40XYT6T6 stem cells cannot be explained by such a mechanism.…”

Section: Resultsmentioning

confidence: 99%

Chromosomal Instability in Unirradiated Hemopoietic Cells Resulting from a Delayed In vivo Bystander Effect of γ Radiation

et al. 2005

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Untargeted effects of ionizing radiation (de novo effects in the unirradiated descendants or neighbors of irradiated cells) challenge widely held views about the mechanisms of radiationinduced DNA damage with implications for the health consequences of radiation exposures particularly in the context of the induction of malignancy. To investigate in vivo untargeted effects of sparsely ionizing (low linear energy transfer) radiation, a congenic sex-mismatch bone marrow transplantation protocol has been used to repopulate the hemopoietic system from a mixture of ;-irradiated and nonirradiated hemopoietic stem cells such that host-, irradiated donor-and unirradiated donor-derived cells can be distinguished. Chromosomal instability in the progeny of irradiated hemopoietic stem cells accompanied by a reduction in their contribution to the repopulated hemopoietic system is consistent with a delayed genomic instability phenotype being expressed in vivo. However, chromosomal instability was also shown in the progeny of the nonirradiated hemopoietic stem cells implicating a bystander mechanism. Studies of the influence of irradiated recipient stromal microenvironment and experiments replacing irradiated cells with irradiated cell-conditioned medium reveal the source of the in vivo bystander effect to be the descendants of irradiated cells, rather than irradiated cell themselves. Thus, it is possible that a radiation-induced genomic instability phenotype in vivo need not necessarily be a reflection of intrinsically unstable cells but the responses to ongoing production of inflammatory-type damaging signals as a long-term unexpected consequence of the initial single radiation exposure. (Cancer Res 2005; 65(13): 5668-73)

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Section: Resultsmentioning

confidence: 99%

Chromosomal Instability in Unirradiated Hemopoietic Cells Resulting from a Delayed In vivo Bystander Effect of γ Radiation

et al. 2005

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“…3,4 Therefore, we investigated ORP-3 gene expression in this population before and after 7-day culture in media containing growth factors that promote the differentiation and proliferation of hematopoietic progenitors. 4,5 Our results indicate that under these culture conditions, ORP-3 gene expression in freshly isolated, uncultured CD34 ϩ cells from UCB and ABM was 2-to 3-fold higher (respectively) than in these same cells after 7 days' culture ( Figure 1B). Investigation of ORP-3 in the more primitive subset of cells defined by the CD34 ϩ 38 Ϫ immunophenotype 6,7 indicates higher expression than in the more mature CD34 ϩ 38 ϩ subset ( Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

ORP-3, a human oxysterol-binding protein gene differentially expressed in hematopoietic cells

Gregorio-King

Collier

McMillan

et al. 2001

Blood

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IntroductionMolecular processes that maintain the stem cell pool and govern the proliferation and differentiation of hematopoietic stem and progenitor cells are widely investigated but incompletely understood. Identification of these genes will facilitate our understanding of hematopoiesis and may be used to improve clinical outcomes.Using differential display-polymerase chain reaction (dd-PCR), we identified a differentially expressed transcript in CD34-enriched populations, with low or absent expression in CD34-depleted populations. Sequencing of this transcript revealed significant homology to oxysterol-binding protein (OSBP). On the basis of ESTs in the GenBank database, a family of up to 8 human genes that code for OSBP-related proteins is postulated to exist. 1 These have been designated OSBP-related proteins (ORPs). A partial sequence for our OSBP-related gene was thus designated ORP-3. 1 Study design CD34 ؉ purificationUmbilical cord blood (UCB) samples were obtained after uncomplicated vaginal or cesarean delivery. Adult bone marrow (ABM) cells were obtained from cell scrapings of discarded rib and femur heads after cardiothoracic or hip-replacement surgery. All samples were donated by volunteers according to approved institutional guidelines. Mononuclear cells were prepared by density-gradient separation through Ficoll-Hypaque (Amersham Pharmacia Biotech, Uppsala, Sweden). CD34 ϩ cells were isolated using a MiniMacs bead separation kit (Miltenyi Biotec, Becton Dickinson, Sunnyvale, CA).Flow cytometric analysis of CD34 ؉ populations and fluorescence-activated cell sorting of CD34 ؉ subsets CD34 ϩ cells were labeled with anti-CD38-fluorescein isothiocyanate, anti-CD34-phycoerythrin, and anti-CD45-PECY5 (Coulter Immunotech, Fullerton, CA). CD34 ϩ purity was determined by flow cytometric analysis (FacsCalibur, Becton Dickinson) following modified ISHAGE guidelines 2 using CELLQuest software (Becton Dickinson). When required, CD34 ϩ 38 Ϫ/ dull cells were sorted using a FacsCalibur Cell Concentrator Sorting Module. Culture of umbilical cord blood CD34 ؉ cellsIn selected experiments, isolated CD34 ϩ cells were cultured for 1 week at 37°C in a humidified atmosphere flushed with 5% CO 2 in air, at a concentration of 0.5 ϫ 10 6 cells/mL in ␣ minimum essential medium (Trace, Noble Park, Victoria, Australia) with 20% fetal bovine serum (CSL Biosciences, Parkville, Victoria, Australia), 2 mM L-glutamine, 200 U/mL penicillin-streptomycin (Sigma, St Louis, MO), 20 ng/mL recombinant human stem cell factor (Amgen, Thousand Oaks, CA), 10 ng/mL IL-1B (Endogen, Woburn, MA), 10 ng/mL IL-3, 10 ng/mL IL-6, and 10 ng/mL G-CSF (Amrad, Boronia, Victoria, Australia). dd-PCRRNA was extracted by RNeasy total RNA isolation kit (Qiagen, Clifton Hill, Victoria, Australia) and was DNase treated (Invitrogen, Carlsbad, CA). Reverse transcription and dd-PCR were carried out as described in the RNAimage Differential Display System (GenHunter, Nashville, TN). We used ABI Prism BigDye Terminator Cycle Sequencing Ready Reaction Kit (PE Appli...

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“…Es konnte in vitro gezeigt werden, dass ein von Makrophagen abstammender Inhibitor der hämatopoeti-schen Stammzellen SCI dem Zytokin MIP-1a ident ist (13,15) und dass SCI/MIP-1a sowohl in den funktionellen als auch antigenen Eigenschaften mit der CFU-S hemmenden Aktivität normaler Knochenmarkszellen verglichen werden kann. Das Molekül MIP-1a hat eine starke Tendenz zu einer nichtkovalenten extensiven Selbstaggregation.…”

Section: Ergebnisseunclassified

Effekte des Chemokins MIP-1α auf Anämie und Entzündungsmechanismen bei Rheumatoider Arthritis

Kullich¹,

Niksic²,

Burmucic³

et al. 2002

Zeitschrift f�r Rheumatologie

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Macrophage inflammatory protein-1alpha (MIP-1alpha) is an interesting chemokine because in addition to its variety proinflammatory activities including chemotaxis and immunomodulation, it is a potent inhibitor of hematopoetic stem cell proliferation. Inhibition of erythroid progenitor cells due to MIP-1alpha or other cytokines can play a role in the pathogenesis of anemia which is one of the most common extra-articular features of active rheumatoid arthritis (RA). In 84 patients with RA, serological and immunological parameters were assessed to detect inflammatory mechanisms and anemia in relation to the serum concentrations of MIP-1alpha. All patients fulfilled the ACR criteria for the diagnosis of a definite or classic RA. We used a quantitative enzyme immuno assay for the detection of MIP-1alpha as well as for the measurement of the acute phase protein serum amyloid A (SAA), the erythropoiesis inducer erythropoietin (EPO) and the transferrin receptor (TfR). The immune activation marker neopterin was measured radioimmunologically. Half of the patients with RA were anemic with hemoglobin values below 12 g/dl. MIP-1alpha was found to be elevated significantly in serum of patients with active rheumatoid arthritis and in patients with anemia. Most of the anemic patients with markedly elevated acute phase reactions had an anemia with chronic diseases and not a functional iron deficiency alone. TfR correlated with EPO. The results show that enhanced expression of MIP-1alpha is indicative of systemic inflammation in RA. Moreover, besides the regulation of inflammatory processes, this chemokine may influence the pathogenesis of anemia in RA patients.

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Haemopoietic stem cells: their heterogeneity and regulation

Cited by 40 publications

References 117 publications

Chromosomal Instability in Unirradiated Hemopoietic Cells Resulting from a Delayed In vivo Bystander Effect of γ Radiation

Chromosomal Instability in Unirradiated Hemopoietic Cells Resulting from a Delayed In vivo Bystander Effect of γ Radiation

ORP-3, a human oxysterol-binding protein gene differentially expressed in hematopoietic cells

Effekte des Chemokins MIP-1α auf Anämie und Entzündungsmechanismen bei Rheumatoider Arthritis

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