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

✍ Scribed by Mohammad Hammoud; Marija Vlaski; Pascale Duchez; Jean Chevaleyre; Xavier Lafarge; Jean-Michel Boiron; Vincent Praloran; Philippe Brunet de la Grange; Zoran Ivanovic

• Publisher: John Wiley and Sons
• Year: 2012
• Tongue: English
• Weight: 421 KB
• Volume: 227
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.23019

✦ Synopsis

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 þ 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 þ 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 þ 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 þ 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 þ 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.