Hematopoietic progenitor cells and interleukin-stimulated endothelium: expansion and differentiation of myeloid precursors

Moldenhauer, Anja; Genter, G; Lun, Andreas; Bal, Gürkan; Kiesewetter, H.; Salama, Abdulgabar

doi:10.1186/1471-2172-9-56

Cited by 16 publications

(34 citation statements)

References 56 publications

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Section: Introductionmentioning

confidence: 84%

“…In brief, 2 Â 10 4 CD34 1 cells isolated from cord blood were cultured in 200 mL of stem cell medium [4]. Potential growth factors (all R&D, www.rndsystems.…”

Section: Quantitative Real-time Rt Pcrmentioning

confidence: 99%

“…Besides brain ECs, IL-stimulated human umbilical cord ECs can also support hematopoiesis [4]. In order to identify new expansion factors, we performed oligonucleotide microarray analyses on IL-1b-stimulated ECs in combination with analyses of the hematopoietic properties of candidate factors using delta and colony assays in combination with flow cytometry.…”

Section: Introductionmentioning

confidence: 99%

“…In previous studies, we demonstrated that ECs stimulated by TNF-a induced the generation of dendritic cells from CD34 1 cells for more than 6 wk [3]. ILs, on the other hand, can also induce the proliferation of hematopoietic and myeloid progenitors [4].So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs [5]. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) [6] …”

mentioning

confidence: 99%

“…Choong et al, for example, discovered proliferin-2 after microarray analyses of several supportive stroma cell lines [20]. Chute et al used a similar approach when they discovered the hematopoietic activity of adrenomedullin expressed by human brain ECs [21].Besides brain ECs, IL-stimulated human umbilical cord ECs can also support hematopoiesis [4]. In order to identify new expansion factors, we performed oligonucleotide microarray analyses on IL-1b-stimulated ECs in combination with analyses of the hematopoietic properties of candidate factors using delta and colony assays in combination with flow cytometry.…”

mentioning

confidence: 99%

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Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Moldenhauer

Futschik

et al. 2011

Eur J Immunol

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The identification of soluble factors involved in stem cell renewal is a major goal in the assessment of the BM niche. We have previously shown that human endothelial cell (EC) supernatants can induce the proliferation of hematopoietic progenitor cells (HPCs), especially after stimulation with IL-1b. To identify new potential growth factors, we compared the expression profile of IL-1b-stimulated ECs over 4, 8 and 16 h with non-stimulated ECs using oligonucleotide microarrays covering more than 46 000 transcripts. Most significant changes were detected after 4 h. Utilization of Gene Ontology annotation for the stimulated EC transcriptome indicated multiple upregulated genes encoding extracellular proteins with a cell-cell signaling function. Using flow cytometry, delta, colony and cobblestone assays, we assessed the proliferative capacities of 11 gene products, i.e. IL-8, IL-32, FGF-18, osteoprotegerin, Gro 1-3, ENA78, GCP-2, CCL2 and CCL20, which are not known to induce HPC expansion. Notably, IL-32 and to a lesser degree osteoprotegerin and Gro 3 significantly induced the proliferation of HPCs. Furthermore, IL-32 attenuated chemotherapy-related BM cytotoxicities by increasing the number of HPCs in mice. Our findings confirm that the combination of microarrays and gene annotation helps to identify new hematopoietic growth factors. Keywords: Endothelial cells . Hematopoietic stem cells . Molecular genetics Supporting Information available online IntroductionEndothelial cells (ECs) have been shown to support the proliferation of hematopoietic CD34 1 progenitor cells by the constitutive production of cytokines [1,2]. In previous studies, we demonstrated that ECs stimulated by TNF-a induced the generation of dendritic cells from CD34 1 cells for more than 6 wk [3]. ILs, on the other hand, can also induce the proliferation of hematopoietic and myeloid progenitors [4].So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs [5]. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) [6] 1774inhibitory factor (LIF) [7] and 9]. Beyond the known cytokine scenario, ECs synthesize multiple other proteins [10], i.e. chemokines of the C-X-C, C-C and TNF receptor superfamily; however, whether these factors can also support hematopoietic progenitor cell (HPC) expansion remains unknown.Notably, microarray technologies monitoring expression changes for thousands of genes have been the basis for several systematic studies of immune and stem cells and their involvement in a variety of processes [11][12][13][14][15]. For example, microarrays of ECs helped to reveal unknown signaling pathways in the endothelial immune cascades [16], specify the role of inflammatory stimuli in neutrophil transmigration [17] and identify the effects of biochemical forces [18]. Microarrays of cultured HPCs also defined detrimental components of engineered extracellular matrices [19]. To use microarrays of feeder cells for the identification of new hematopoietic growth factors is another aspect. Choong e...

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Section: Introductionmentioning

confidence: 84%

“…In brief, 2 Â 10 4 CD34 1 cells isolated from cord blood were cultured in 200 mL of stem cell medium [4]. Potential growth factors (all R&D, www.rndsystems.…”

Section: Quantitative Real-time Rt Pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Moldenhauer

Futschik

et al. 2011

Eur J Immunol

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Co‐cultured hBMSCs and HUVECs on human bio‐derived bone scaffolds provide support for the long‐term ex vivo culture of HSC/HPCs

Huang

Bao-cheng

et al. 2016

J Biomedical Materials Res

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In order to closely mimic a multi-cell state in hematopoietic stem/progenitor cells (HSC/HPCs) vascular niche, we co-cultured human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) without any cytokines as feeder cells and applied bio-derived bone from human femoral metaphyseal portion as scaffold to develop a new HSC/HPCs three-dimensional culture system (named 3D-Mix cultures). Scanning electron and fluorescent microscopy showed excellent biocompatibility of bio-derived bone to hBMSCs and HUVECs in vitro. Flow cytometry analysis and quantitative real-time polymerase chain reaction (qPCR) assay of p21 expression demonstrated that 3D-Mix could promote self-renewal and ex vivo expansion of HSCs/HPCs significantly higher than 3D-hMSC and 3D-HUVEC. Long-term culture initiating cell (LTC-IC) confirmed that 3D-Mix had the most powerful activity of maintaining multipotent differentiation of primitive cell subpopulation in HSCs. The nonobese diabetic/severe combined immunodeficiency (NOD/SCID) repopulating cell (SRC) assay demonstrated that 3D-Mix promoted the expansion of long-term primitive transplantable HSCs. qPCR of alkaline phosphatase (ALP) and osteocalcin (OC) demonstrated that HUVECs enhanced the early osteogenic differentiation of BMSCs. Western blot and qPCR revealed that HUVECs activated Wnt/β-catenin signaling in hBMSCs inducing Notch signal activation in HSCs. Our study indicated that interaction between hMSCs and HUVECs may have a critical role in to influent on HSCs/HPCs fate in vitro. These results demonstrated that the 3D-Mix have the ability to support the maintenance and proliferation of HSCs/HPCs in vitro.

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Antiinflammatory effects of Epimedium brevicornum water extract on lipopolysaccharide‐activated RAW264.7 macrophages

Yuk¹,

Lim²,

Lee³

et al. 2010

Phytotherapy Research

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Epimedium brevicornum Maxim (Berberidaceae) possesses estrogenic properties. It is one of the most widespread herbal remedies used in Oriental medicine. The present study investigated the effects of Epimedium brevicornum water extract (EB) on proinflammatory mediators secreted from lipopolysaccharide (LPS)-induced RAW264.7 macrophages. EB significantly inhibited the production of nitric oxide (NO), interleukin (IL)-3, IL-10, IL-12p40, interferon-inducible protein-10, keratinocyte-derived chemokine, vascular endothelial growth factor, monocyte chemotactic protein-1 and granulocyte macrophage-colony stimulating factor in LPS-induced RAW264.7 cells at concentrations of 25, 50, 100 and 200 μg/mL (p < 0.05). These results suggest that EB has antiinflammatory activity related to its inhibition of NO, cytokine, chemokine and growth factor production in macrophages.

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Hematopoietic progenitor cells and interleukin-stimulated endothelium: expansion and differentiation of myeloid precursors

Cited by 16 publications

References 56 publications

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Co‐cultured hBMSCs and HUVECs on human bio‐derived bone scaffolds provide support for the long‐term ex vivo culture of HSC/HPCs

Antiinflammatory effects of Epimedium brevicornum water extract on lipopolysaccharide‐activated RAW264.7 macrophages

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