The effect of stem cell proliferation regulators demonstrated with an in vitro assay

Pragnell, Ian B.; Wright, E. A.; Lorimore, SA; Adam, Julie; Rosendaal, Martin; DeLamarter, JF; Freshney, M; Eckmann, Lars; Sproul, Anne M.; Wilkie, N. M.

doi:10.1182/blood.v72.1.196.bloodjournal721196

Cited by 8 publications

(13 citation statements)

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“…Finally, MIP-1α and MIP-1β exibit activity on hematopoiesis. MIP-1α inhibits the primitive bone marrow progenitors as defined by spleen colony assay (CFU-S), and MIP-1β prevents the inhibitory activity of MIP-1α ( 13 , 14 ). Both MIP-1α and MIP-1β inhibit megakaryocyte development ( 15 ).…”

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confidence: 99%

Molecular and Functional Characterization of Two Novel Human C-C Chemokines as Inhibitors of Two Distinct Classes of Myeloid Progenitors

Patel

Kreider

et al. 1997

The Journal of Experimental Medicine

227

152

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Two novel human β-chemokines, Ckβ-8 or myeloid progenitor inhibitory factor 1 (MPIF-1), and Ckβ-6 or MPIF-2, were discovered as part of a large scale cDNA sequencing effort. The MPIF-1 and MPIF-2 cDNAs were isolated from aortic endothelium and activated monocyte libraries, respectively. Both of the cDNAs were cloned into a baculovirus vector and expressed in insect cells. The mature recombinant MPIF-1 protein consists of 99 amino acids and is most homologous to macrophage inflammatory protein (MIP)-1α, showing 51% identity. It displays chemotactic activity on resting T lymphocytes and monocytes, a minimal but significant activity on neutrophils, and is negative on activated T lymphocytes. MPIF-1 is also a potent suppressor of bone marrow low proliferative potential colony-forming cells, a committed progenitor that gives rise to granulocyte and monocyte lineages. The mature recombinant MPIF-2 has 93 amino acid residues and shows 39 and 42% identity with monocyte chemoattractant protein (MCP)-3 and MIP-1α, respectively. It displays chemotactic activity on resting T lymphocytes, a minimal activity on neutrophils, and is negative on monocytes and activated T lymphocytes. On eosinophils, MPIF-2 produces a transient rise of cytosolic Ca2+ and uses the receptor for eotaxin and MCP-4. In hematopoietic assays, MPIF-2 strongly suppressed the colony formation by the high proliferative potential colony-forming cell (HPP-CFC), which represents a multipotential hematopoietic progenitor.

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confidence: 99%

Molecular and Functional Characterization of Two Novel Human C-C Chemokines as Inhibitors of Two Distinct Classes of Myeloid Progenitors

Patel

Kreider

et al. 1997

The Journal of Experimental Medicine

227

152

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“…MIP-la was termed stem cell inhibitor based on its ability to inhibit in vitro the cycling of CFU-S and CFU-A, a progenitor forming macroscopic colonies composed primarily of macrophages and sharing properties in common with CFU-S?. 6 In vivo, in mice treated once with phenylhydrazine or 5-fluorouracil (5-FU), a single inoculation of MIP-1 a reduced significantly the proportion of CFU-S and CFU-A in S-phase, as assessed by the sensitivity of the cells to the cell-cycle-specific cytotoxic drug cytosine arabinoside (Ara-c).' This effect resulted in the protection of a number of CFU-S and CFU-A in animals receiving two consecutive injections of Ara-C or hydroxyurea within a few h o~r s .~.~ The existing evidence demonstrating that MIP-1 a might be an inhibitor of stem cell cycling is therefore based on indirect assessment of stem cell responses using assays detecting more mature progenitors.…”

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confidence: 99%

Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo

Quesniaux

Graham

Pragnell

et al. 1993

Blood

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A macrophage-derived inhibitor of early hematopoietic progenitors (colony-forming unit-spleen, CFU-A) called stem cell inhibitor was found to be identical to macrophage inflammatory protein-1 alpha (MIP-1 alpha). We investigated the effect of MIP-1 alpha on the earliest stem cells that sustain long-term hematopoiesis in vivo in a competitive bone marrow repopulation assay. Because long-term reconstituting (LTR) stem cells are normally quiescent, an in vivo model was first developed in which they are triggered to cycle. A first 5-fluorouracil (5-FU) injection was used to eliminate later progenitors, causing the LTR stem cells, which are normally resistant to 5-FU, to enter the cell cycle and become sensitive to a second 5-FU injection administered 5 days later. Human MIP-1 alpha administered from day 0 to 7 was unable to prevent the depletion of the LTR stem cells by the second 5-FU treatment, as observed on day 7 in this model, suggesting that the LTR stem cells were not prevented from being triggered into cycle despite the MIP-1 alpha treatment. However, the MIP-1 alpha protocol used here did substantially decrease the number of more mature hematopoietic progenitors (granulocyte-macrophage colony-forming cells [CFC], burst- forming unit-erythroid, CFCmulti, and preCFCmulti) recovered in the bone marrow shortly after a single 5-FU injection. In vitro, MIP-1 alpha had no inhibitory effect on the ability of these progenitors to form colonies. This study confirms the in vivo inhibitory effect of MIP- 1 alpha on subpopulations of hematopoietic progenitors that are activated in myelodepressed animals. However, MIP-1 alpha had no effect on the long-term reconstituting stem cells in vivo under conditions in which it effectively reduced all later progenitors.

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“…The canonical function of chemokines is to activate or attract to the sites of inflammation effector cells, such as lymphocytes, monocytes, neutrophils, and eosinophils [ 33 ], but a subset of these proteins also regulate HSPCs [ 34 , 35 , 36 , 37 ]. CCL24, which specifically blocks the differentiation of myeloid progenitors [ 38 ] and CCL3, which binds the same receptors as several of the chemokines that we identified in this report, control myeloid lineage differentiation and the size of the HSPC pool [ 39 ].…”

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confidence: 99%

HbF Levels in Sickle Cell Disease Are Associated with Proportion of Circulating Hematopoietic Stem and Progenitor Cells and CC-Chemokines

Minniti

Tolu

Wang

et al. 2020

Cells

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The concentration of circulating hematopoietic stem and progenitor cells has not been studied longitudinally. Here, we report that the proportions of Lin-CD34+38- hematopoietic multipotent cells (HMCs) and of Lin-CD34+CD38+ hematopoietic progenitors cells (HPCs) are highly variable between individuals but stable over long periods of time, in both healthy individuals and sickle cell disease (SCD) patients. This suggests that these proportions are regulated by genetic polymorphisms or by epigenetic mechanisms. We also report that in SCD patients treated with hydroxyurea, the proportions of circulating HMCs and HPCs show a strong positive and negative correlation with fetal hemoglobin (HbF) levels, respectively. Titration of 65 cytokines revealed that the plasma concentration of chemokines CCL2, CCL11, CCL17, CCL24, CCL27, and PDGF-BB were highly correlated with the proportion of HMCs and HPCs and that a subset of these cytokines were also correlated with HbF levels. A linear model based on four of these chemokines could explain 80% of the variability in the proportion of circulating HMCs between individuals. The proportion of circulating HMCs and HPCs and the concentration of these chemokines might therefore become useful biomarkers for HbF response to HU in SCD patients. Such markers might become increasingly clinically relevant, as alternative treatment modalities for SCD are becoming available.

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The effect of stem cell proliferation regulators demonstrated with an in vitro assay

Cited by 8 publications

References 0 publications

Molecular and Functional Characterization of Two Novel Human C-C Chemokines as Inhibitors of Two Distinct Classes of Myeloid Progenitors

Molecular and Functional Characterization of Two Novel Human C-C Chemokines as Inhibitors of Two Distinct Classes of Myeloid Progenitors

Use of 5-fluorouracil to analyze the effect of macrophage inflammatory protein-1 alpha on long-term reconstituting stem cells in vivo

HbF Levels in Sickle Cell Disease Are Associated with Proportion of Circulating Hematopoietic Stem and Progenitor Cells and CC-Chemokines

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