Interleukin 3 Improves the Ex Vivo Expansion of Primitive Human Cord Blood Progenitor Cells and Maintains the Engraftment Potential of SCID Repopulating Cells
Article first published online: 1 JUL 2001
Copyright © 2001 AlphaMed Press
Volume 19, Issue 4, pages 313–320, July 2001
How to Cite
Roβmanith, T., Schröder, B., Bug, G., Müller, P., Klenner, T., Knaus, R., Hoelzer, D. and Ottmann, O. G. (2001), Interleukin 3 Improves the Ex Vivo Expansion of Primitive Human Cord Blood Progenitor Cells and Maintains the Engraftment Potential of SCID Repopulating Cells. STEM CELLS, 19: 313–320. doi: 10.1634/stemcells.19-4-313
- Issue published online: 1 JAN 2009
- Article first published online: 1 JUL 2001
- Manuscript Accepted: 15 MAR 2001
- Manuscript Received: 21 DEC 2000
- Stem cells;
- Umbilical cord blood;
- Ex vivo expansion;
- NOD/SCID model;
- Interleukin 3
In umbilical cord blood (UCB) transplantation, the number of nucleated cells per kilogram is a major predictive and critical factor of hematopoietic recovery. Thus, ex vivo expansion of hematopoietic UCB progenitors could potentially accelerate engraftment. Whereas Flt-3 ligand (FL), stem cell factor (SCF), and thrombopoietin (TPO) are considered indispensable, the role of interleukin 3 (IL-3) is still controversial: it has been reported either to support or abrogate the reconstituting ability of stem cells. By adding IL-3 we aimed to enhance the amplification of early and committed progenitor cells without impairing the long-term engraftment of stem cells.
Demonstrating a positive impact of IL-3 on the proliferation of all progenitor subsets, the amplification of CD34+ UCB cells was increased 20.9-fold ± 5.4 (mean ± standard error) in serum-free culture with FL, SCF, TPO, and IL-3 as opposed to 9.3-fold ± 3.2 without IL-3 after 7 days. If IL-3 was included, primitive long-term culture-initiating cells and committed colony-forming cells were expanded 16.3-fold ± 5.5 and 18.1-fold ± 2.4, respectively, compared to 12.6-fold ± 5.6 and 9.1-fold ± 2.0 without IL-3.
Analysis of cultured CD34+ UCB cells in sublethally irradiated nonobese diabetic/severe combined immunodeficient mice confirmed that cultured cells had preserved their repopulating potential. After 6 weeks, all mice showed multilineage engraftment with their bone marrow containing an average of 45% human CD45+ cells of the unmanipulated sample, 43% of cells after culture in the presence of IL-3, and 27% of cells after culture without IL-3. In combination with early acting cytokines, IL-3 therefore improves the ex vivo expansion of UCB stem and progenitor cells without impairing their engraftment potential.