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Issue 7, 2010
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Systematic delineation of optimal cytokine concentrations to expand hematopoietic stem/progenitor cells in co-culture with mesenchymal stem cells

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Abstract

The major obstacle to the widespread use of umbilical cord blood (UCB) in hematopoietic stem/progenitor (HSC) cell therapy is the low cell dose available. A cytokine cocktail for the ex vivo expansion of UCB HSC, in co-culture with a bone marrow (BM) mesenchymal stem cells (MSC)-derived stromal layer was optimized using an experimental design approach. Proliferation of total cells (TNC), stem/progenitor cells (CD34+) and colony-forming units (CFU) was assessed after 7 days in culture, while sole and interactive effects of each cytokine on HSC expansion were statistically determined using a two-level Face-Centered Cube Design. The optimal cytokine cocktail obtained for HSC-MSC co-cultures was composed by SCF, Flt-3L and TPO (60, 55 and 50 ng mL−1, respectively), resulting in 33-fold expansion in TNC, 17-fold in CD34+ cells, 3-fold in CD34+CD90+ cells and 21-fold in CFU-MIX. More importantly, these short-term expanded cells preserved their telomere length and extensively generated cobblestone area-forming cells (CAFCs) in vitro. The statistical tools used herein contributed for the rational delineation of the cytokine concentration range, in a cost-effective way, while systematically addressing complex cytokine-to-cytokine interactions, for the efficient HSC expansion towards the generation of clinically significant cell numbers for transplantation.

Graphical abstract: Systematic delineation of optimal cytokine concentrations to expand hematopoietic stem/progenitor cells in co-culture with mesenchymal stem cells

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Publication details

The article was received on 28 Oct 2009, accepted on 12 Mar 2010 and first published on 27 Apr 2010


Article type: Paper
DOI: 10.1039/B922637K
Citation: Mol. BioSyst., 2010,6, 1207-1215
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    Systematic delineation of optimal cytokine concentrations to expand hematopoietic stem/progenitor cells in co-culture with mesenchymal stem cells

    P. Z. Andrade, F. dos Santos, G. Almeida-Porada, C. Lobato da Silva and J. M. S. Cabral, Mol. BioSyst., 2010, 6, 1207
    DOI: 10.1039/B922637K

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