Tumor Necrosis Factor Alpha Enhances the Adenoviral Transduction of CD34<sup>+</sup>Hematopoietic Progenitor Cells

Moldenhauer, Anja; Shieh, J-H; Salama, Abdulgabar; Moore, Malcolm A.S.

doi:10.1634/stemcells.22-3-283

Cited by 9 publications

(11 citation statements)

References 32 publications

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“…Cord blood specimens were collected from full-term deliveries, after informed consent was obtained from the mothers, and HPCs were immunomagnetically isolated as previously described [52]. This study was approved by the ethical review board of the Charité.…”

Section: Cord Blood and Hpc Selectionmentioning

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: Cord Blood and Hpc Selectionmentioning

confidence: 99%

“…The morphology of the cells was assessed after Diffquik staining. Excessive cells were analyzed for the presence of CD34 and CD45 by flow cytometry [52], for their clonogenic efficiency by methylcellulose colony assays [59] and for their BM reconstitution capacity by cobblestone assays on the murine stroma cell line . …”

mentioning

confidence: 99%

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Moldenhauer

Futschik

et al. 2011

Eur J Immunol

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“…15 The idea of antiapoptotic factors in samples stored at RT is also supported by the apoptosis analysis and clonogenicity data: storage at RT did not increase the apoptosis rate, while after 24 h at 4 1C more cells stained positive for annexin, a marker for early apoptosis. 11 The apoptosis rate decreased with storage time indicating that early apoptotic cells probably died off within 24 h and were removed by Ficoll the following day. This could also explain the reincrease of CFU-GM from 24 to 48 h of storage, as apoptosing cells were not plated.…”

Section: Discussionmentioning

confidence: 99%

“…CD34 þ HPCs were immunomagnetically selected as described previously. 11 Baseline values represent results from CD34 þ cells isolated from cord blood immediately after harvest (ficolled within 1 h).…”

Section: Cord Blood Units and Hpcs Selectionmentioning

confidence: 99%

“…After 2 weeks in culture, the number of hematopoietic colonies was counted and the plating efficiencies were calculated. 11 Total number of colonies represent the number of counted colonies per 1000 plated CD34 þ cells multiplied with the total number of CD34 þ cells divided by 1000. This represents the number of colonies that would be obtained if all isolated cells were plated.…”

Section: Clonogenic Assaysmentioning

confidence: 99%

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Optimum storage conditions for cord blood-derived hematopoietic progenitor cells prior to isolation

Moldenhauer

Wolf

Habermann

et al. 2007

Bone Marrow Transplant

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Optimum storage conditions of cord blood-derived hematopoietic progenitor cells before isolation remain unknown. We therefore evaluated CD34 þ cells isolated from cord blood units (n ¼ 57) within 1 h after collection and following storage for 24, 48 and 72 h at either room temperature (RT) or 4 1C. Isolated CD34 þ cells were analyzed for their cell count, immunophenotype, apoptosis rate, clonogenicity and transmigration capacity in response to stromaderived factor 1a using direct-paired comparisons (n ¼ 27). CD34 þ , CD133 þ and CD45 þ positivity after isolation remained the same under all conditions. After 24 h, CD34 þ cell counts and numbers of CFU-GM colonies dropped regardless of the storage temperature. After 48 h, the number of CD34 þ cells increased compared to 24 h, if the cord blood had been stored at RT resulting in almost three times more CD34 þ cells than at 4 1C. These cells had a lower early apoptosis rate and formed four times more BFU-E than those stored at 4 1C with equivalent plating efficiencies. CD34 þ cells kept at RT for 48 h had the highest transmigration capacities, which paralleled an increased CXCR-4 expression. Cord blood should be stored at RT before CD34 þ isolation and a storage time for 48 h should be preferred to 24 h.

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Expression, Purification, and Characterization of a Novel Soluble Form of Human Delta-like-1

Zhao

Guo

et al. 2009

Appl Biochem Biotechnol

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The notch signaling pathway plays an important role in inhibiting cell differentiation and enhancing the repopulation capability of hematopoietic stem/progenitor cells. In this study, we developed rhDSL, a novel soluble form of Notch ligand Delta-like-1, which contains the DSL domain and the N-terminal sequence of the ligand, and investigated its function in ex vivo expansion of human umbilical cord blood (UCB)-primitive hematopoietic cells. The coding sequence for rhDSL was cloned into a pQE30 vector, and the recombinant rhDSL, fused with a 6x His tag, was expressed in Escherichia coli as inclusion bodies after isopropyl beta-D-thiogalactoside induction. After renaturing by dilutions, the protein was purified through anion exchange followed by affinity chromatography. The purity of rhDSL protein was more than 99% with very low endotoxin. In combination with human c-kit ligand, the effect of rhDSL on ex vivo expansion of UCB CD34(+) cells was found to be optimal at 1.5 microg/ml of rhDSL. The rhDSL protein might therefore be a potential supplement for the expansion of UCB-primitive hematopoietic cells.

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Tumor Necrosis Factor Alpha Enhances the Adenoviral Transduction of CD34⁺Hematopoietic Progenitor Cells

Abstract: The purpose of this study was to improve the transduction efficiency of adenoviral vectors (Ad) in human CD34+ hematopoietic progenitor cells. CD34 + cells from cord blood or mobilized peripheral blood were incubated with tumor necrosis factor-alpha (TNF-α α).

Cited by 9 publications

References 32 publications

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Optimum storage conditions for cord blood-derived hematopoietic progenitor cells prior to isolation

Expression, Purification, and Characterization of a Novel Soluble Form of Human Delta-like-1

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Tumor Necrosis Factor Alpha Enhances the Adenoviral Transduction of CD34+Hematopoietic Progenitor Cells

Abstract: The purpose of this study was to improve the transduction efficiency of adenoviral vectors (Ad) in human CD34+ hematopoietic progenitor cells. CD34 + cells from cord blood or mobilized peripheral blood were incubated with tumor necrosis factor-alpha (TNF-α α).

Cited by 9 publications

References 32 publications

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Optimum storage conditions for cord blood-derived hematopoietic progenitor cells prior to isolation

Expression, Purification, and Characterization of a Novel Soluble Form of Human Delta-like-1

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Tumor Necrosis Factor Alpha Enhances the Adenoviral Transduction of CD34⁺Hematopoietic Progenitor Cells