Interleukin‐6 (IL‐6) and low O<sub>2</sub> concentration (1%) synergize to improve the maintenance of hematopoietic stem cells (pre‐CFC)

Kovačević-Filipović, Milica; Petakov, M; Hermitte, Francis; Debeissat, Christelle; Krstić, Aleksandra; Jovčić, Gordana; Bugarski, D; Lafarge, Xavier; Milenković, P; Perreten, Vincent; Ivanović, Zoran

doi:10.1002/jcp.21003

Cited by 39 publications

(25 citation statements)

References 51 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-6 is also induced by hypoxia in macrophages 5,28 and improves the survival and maintenance of hematopoietic stem cells in low oxygen. 29 Tissue pO 2 levels are normally in the range 5-12%. In bone marrow aspirates from healthy adult donors, pO 2 is about 6.5% (although such measurements necessarily represent an average value).…”

Section: Resultsmentioning

confidence: 99%

Hypoxia stimulates osteoclast formation from human peripheral blood

Utting

Flanagan

Brandao-Burch

et al. 2010

Cell Biochemistry & Function

View full text Add to dashboard Cite

Active pathological bone destruction in humans often occurs in locations where oxygen tension (pO(2)) is likely to be low, for example, at the sites of tumours, inflammation, infections and fractures, or the poorly vascularized yellow fatty marrow of the elderly. We examined the effect of pO(2) on formation of osteoclasts, the cells responsible for bone resorption, in 14-day cultures of normal human peripheral blood mononuclear cells (hPBMCs) on ivory discs. Hypoxia (1-2% O(2)) caused threefold increases in the number of osteoclasts formed, compared with 20% O(2). Hypoxia also caused a twofold increase in the number of nuclei per osteoclast, leading to stimulations of resorption pit formation of up to 10-fold. Exposure to hypoxia led to stabilization of the hypoxia-inducible factors, HIF1alpha and HIF2alpha, and upregulation of vascular endothelial growth factor and interleukin-6 expression by hPBMCs. These findings help explain why extravasation of mononuclear precursors into relatively O(2)-deficient bone microenvironments could result in osteoclast formation and suggest a new mechanism for the bone loss associated with the pathophysiological conditions where hypoxia commonly occurs.

show abstract

Section: Resultsmentioning

confidence: 99%

Hypoxia stimulates osteoclast formation from human peripheral blood

Utting

Flanagan

Brandao-Burch

et al. 2010

Cell Biochemistry & Function

View full text Add to dashboard Cite

show abstract

“…The production of committed progenitors during a long-term secondary culture (C2) reflects the presence and quantity of a primitive population situated between progenitors and stem cells (pre-CFC) in C1 (Ivanovic et al, 2000(Ivanovic et al, , 2002Kovacevic-Filipovic et al, 2007). C1 cells (total Day-10 progeny of 20,000 CD34…”

Section: Pre-cfcs (Primitive Progenitors) Assaymentioning

confidence: 99%

Combination of low O₂ concentration and mesenchymal stromal cells during culture of cord blood CD34⁺ cells improves the maintenance and proliferative capacity of hematopoietic stem cells

Hammoud

Vlaški

Duchez

et al. 2012

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

The physiological approach suggests that an environment associating the mesenchymal stromal cells (MSC) and low O(2) concentration would be most favorable for the maintenance of hematopoietic stem cells (HSCs) in course of ex vivo expansion of hematopoietic grafts. To test this hypothesis, we performed a co-culture of cord blood CD34(+) cells with or without MSC in presence of cytokines for 10 days at 20%, 5%, and 1.5% O(2) and assessed the impact on total cells, CD34(+) cells, committed progenitors (colony-forming cells-CFC) and stem cells activity (pre-CFC and Scid repopulating cells-SRC). Not surprisingly, the expansion of total cells, CD34(+) cells, and CFC was higher in co-culture and at 20% O(2) compared to simple culture and low O(2) concentrations, respectively. However, co-culture at low O(2) concentrations provided CD34(+) cell and CFC amplification similar to classical culture at 20% O(2) . Interestingly, low O(2) concentrations ensured a better pre-CFC and SRC preservation/expansion in co-culture. Indeed, SRC activity in co-culture at 1.5% O(2) was higher than in freshly isolated CD34(+) cells. Interleukin-6 production by MSC at physiologically low O(2) concentrations might be one of the factors mediating this effect. Our data demonstrate that association of co-culture and low O(2) concentration not only induces sufficient expansion of committed progenitors (with respect to the classical culture), but also ensures a better maintenance/expansion of hematopoietic stem cells (HSCs), pointing to the oxygenation as a physiological regulatory factor but also as a cell engineering tool.

show abstract

“…This assay estimates the culture-repopulating power of normal 8,[10][11][12][13] or leukemic 1,2,7 hematopoietic cells undergoing a selection treatment (e.g. hypoxia) in a primary liquid culture (LC1) by means of their wash and transfer in fresh medium to non-selective conditions (e.g.…”

Section: The Culture-repopulating Ability (Cra) Assaymentioning

confidence: 99%

Glucose availability in hypoxia regulates the selection of chronic myeloid leukemia progenitor subsets with different resistance to imatinib-mesylate

Giuntoli¹,

Tanturli²,

Gesualdo³

et al. 2010

Haematologica

View full text Add to dashboard Cite

BackgroundIncubation of chronic myeloid leukemia cells in hypoxia inhibits growth and selects BCR/Ablindependent cells with stem cell properties which are refractory to imatinib-mesylate. This study aimed to characterize the relationship of this refractoriness with glucose availability in the environment. Design and MethodsK562 or primary chronic myeloid leukemia cells were cultured at 0.1% O2, different cell densities and glucose concentrations. The stem and progenitor cell potential of these cultures at different times of incubation in relation to BCR/Ablprotein expression and sensitivity to imatinibmesylate was explored by transferring cells to growth-permissive secondary cultures in normoxia, according to the Culture-Repopulating Ability assay methodology. ResultsHypoxia-resistant cells maintained BCR/Ablprotein expression until glucose was no longer available in primary hypoxic cultures, where glucose availability appeared to regulate cell number and the balance between the enrichment of cells with kinetic properties typical of stem or progenitor cells. Cells surviving merely hypoxic conditions were, upon transfer to secondary cultures, immediately available for numerical expansion due to the maintained BCR/Ablprotein expression, and were consequently sensitive to imatinib-mesylate. Instead, BCR/Ablprotein-negative cells selected in primary cultures under oxygen/glucose shortage underwent a delayed numerical expansion in secondary cultures, which was completely refractory to imatinib-mesylate. Cells with the latter properties were also found in primary chronic myeloid leukemia explants. ConclusionsGlucose shortage in hypoxia was shown to represent the condition selecting BCR/Ablprotein-negative cells refractory to imatinib-mesylate from either chronic myeloid leukemia lines or patients. These cells, exhibiting stem cell properties in vitro, are metabolically suited to home to stem cell niches in vivo and so may represent the chronic myeloid leukemia cell subset responsible for minimal residual disease.Key words: imatinib-mesylate, chronic myeloid leukemia, glucose, hypoxia.Citation: Giuntoli S, Tanturli M, Di Gesualdo F, Barbetti V, Rovida E, and Dello Sbarba P. Glucose availability in hypoxia regulates the selection of chronic myeloid leukemia progenitor subsets with different resistance to imatinib-mesylate. Haematologica 2011;96(2):204-212. doi:10.3324/haematol.2010 Glucose availability in hypoxia regulates the selection of chronic myeloid leukemia progenitor subsets with different resistance to imatinib-mesylate

show abstract

Interleukin‐6 (IL‐6) and low O₂ concentration (1%) synergize to improve the maintenance of hematopoietic stem cells (pre‐CFC)

Cited by 39 publications

References 51 publications

Hypoxia stimulates osteoclast formation from human peripheral blood

Hypoxia stimulates osteoclast formation from human peripheral blood

Combination of low O₂ concentration and mesenchymal stromal cells during culture of cord blood CD34⁺ cells improves the maintenance and proliferative capacity of hematopoietic stem cells

Glucose availability in hypoxia regulates the selection of chronic myeloid leukemia progenitor subsets with different resistance to imatinib-mesylate

Contact Info

Product

Resources

About

Interleukin‐6 (IL‐6) and low O2 concentration (1%) synergize to improve the maintenance of hematopoietic stem cells (pre‐CFC)

Cited by 39 publications

References 51 publications

Hypoxia stimulates osteoclast formation from human peripheral blood

Hypoxia stimulates osteoclast formation from human peripheral blood

Combination of low O2 concentration and mesenchymal stromal cells during culture of cord blood CD34+ cells improves the maintenance and proliferative capacity of hematopoietic stem cells

Glucose availability in hypoxia regulates the selection of chronic myeloid leukemia progenitor subsets with different resistance to imatinib-mesylate

Contact Info

Product

Resources

About

Interleukin‐6 (IL‐6) and low O₂ concentration (1%) synergize to improve the maintenance of hematopoietic stem cells (pre‐CFC)

Combination of low O₂ concentration and mesenchymal stromal cells during culture of cord blood CD34⁺ cells improves the maintenance and proliferative capacity of hematopoietic stem cells