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

✍ Scribed by Milica Kovačević-Filipović; Marijana Petakov; Francis Hermitte; Christelle Debeissat; Aleksandra Krstić; Gordana Jovčić; Dijana Bugarski; Xavier Lafarge; Pavle Milenković; Vincent Praloran; Zoran Ivanović

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 320 KB
• Volume: 212
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21003

✦ Synopsis

Abstract

Low O~2~ concentration (1%) favors the self‐renewal of hematopoietic stem cells and inhibits committed progenitors (CFC). Since IL‐6 influences both stem cells and committed progenitors at 20% O~2~, we studied its effects in cultures at 1% O~2~. The pre‐CFC activity in Lin− population of mouse bone marrow was analyzed following 10 days of serum‐free culture in medium (LC1) supplemented with IL‐3 with and without IL‐6, at 20 and 1% O~2~ and phenotypic differentiation and proliferative history monitored. The IL‐6 receptor expression and initiation of VEGF‐A synthesis were also investigated. At 20% O~2~, the effects of IL‐6 on pre‐CFC were negligible but effects on CFC were apparent; conversely, at 1% O~2~, the IL‐6 enhances activity of pre‐CFC but not of CFC. Unlike at 20% O~2~, at 1% O~2~ a subpopulation of cells remained Lin− in spite of extensive proliferation. However, the absolute number of Lin− cells, did not correlate with pre‐CFC activity. A relative increase in VEGF transcripts at 1% O~2~ in presence of IL‐3 alone was enhanced by the addition of IL‐6. IL‐6 enhanced pre‐CFC activity at 1% O~2~ and this was correlated to the induction of VEGF. These data reinforce the concept that physiologically low oxygenation of bone marrow is a regulator of stem cell maintenance. Since the 20% O~2~ does not exist in tissues in vivo, further studies in vitro at lower O~2~ concentrations should revise our knowledge relating to cytokine effects on stem and progenitor cells. J. Cell. Physiol. 212: 68–75, 2007. © 2007 Wiley‐Liss, Inc.