Impact of oxygen concentration on growth of mesenchymal stromal cells from the marrow of patients with chronic lymphocytic leukemia.

Abstract

Chronic lymphocytic leukemia (CLL) cells interact in the marrow with mesenchymal stromal cells (MSCs), which can enhance CLL-cells’ resistance to spontaneous or drug-induced apoptosis. Here we examined the effect of oxygen on the growth and function of MSCs from marrow aspirates of CLL patients. Cultures in ambient oxygen provided for poor recovery and growth of MSCs, which developed features of cell senescence. However, MSCs were propagated readily from the same cells when they were cultured at a physiologic oxygen concentration of 5%. Such MSCs promoted short-term CLL-cell survival in either 5% or ambient O2. However, longer-term CLL-cell survival was enhanced when the cocultures were maintained in 5% O2 versus 21% O2 because of increased MSC proliferation and production of soluble prosurvival factors, such as CXCL12. This study establishes the importance of physiologic oxygen concentration in the propagation and function of MSCs derived from marrow aspirates of CLL patients in vitro.

• Authors: Jessie-F Fecteau, Davorka Messmer, Suping Zhang, Bing Cui, Liguang Chen, Thomas J Kipps
• Journal: Blood (Blood) Vol. 121 Issue 6 Pg. 971-4 (Feb 07 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23255557 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD19
• CD5 Antigens
• CXCL12 protein, human
• CXCR4 protein, human
• Chemokine CXCL12
• Receptors, CXCR4
• Oxygen

Topics

• Antigens, CD19 (metabolism)
• Bone Marrow Cells (drug effects, metabolism)
• CD5 Antigens (metabolism)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Cellular Senescence (drug effects)
• Chemokine CXCL12 (metabolism)
• Coculture Techniques
• Dose-Response Relationship, Drug
• Flow Cytometry
• Humans
• Immunoblotting
• Immunophenotyping
• Leukemia, Lymphocytic, Chronic, B-Cell (blood, metabolism, pathology)
• Mesenchymal Stem Cells (drug effects, metabolism)
• Oxygen (pharmacology)
• Receptors, CXCR4 (metabolism)
• Tumor Cells, Cultured