Author(s): Drouet M, Herodin F, Norol F, Mourcin F, Mayol JF
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Abstract Ex vivo expansion is a new strategy for hematopoietic stem and progenitor cell transplantation based on cytokine-induced amplification to produce grafts of controlled maturity. If the cell cycle position of CD34(+) cells has been reported to govern their engraftment potential, the respective role of stem and progenitor cells in short- and long-term hematopoietic recovery remains debated. Studies focused on long-term engraftment potential suggest impairment when using cultured grafts, but the capacity to sustain short-term recovery is still controverted. The aim of this study was: A) to evaluate the consequences of cell cycle activation on short and long-term engraftment capacity, and B) to determine if cell cycle status of grafts could predict hematopoietic recovery. We showed in a nonhuman primate model of autologous peripheral blood stem and progenitor cell transplantation that cell cycle activation of CD34(+) cells in the presence of stem cell factor + FLT3-ligand + thrombopoietin + interleukin 3 (six days of culture) which induced G1 and S/G2/M cell amplification (G0: 6.1\% +/- 2.8\%; G0/G1: 64.2\% +/- 7.2\%; S/G2/M: 30.4\% +/- 7.3\% respectively of expanded CD34(+) cells on average) resulted in the acceleration of short-term granulocyte recovery. By contrast, G0/G1 and S/G2/M cell content of expanded grafts did not correlate with short- or long-term engraftment.
This article was published in Stem Cells
and referenced in Journal of Stem Cell Research & Therapy