Cell cycle activation of peripheral blood stem and progenitor cells expanded ex vivo with SCF, FLT-3 ligand, TPO, and IL-3 results in accelerated granulocyte recovery in a baboon model of autologous transplantation but G0/G1 and S/G2/M graft cell content does not correlate with transplantability.
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.
Drouet
M
M
Experimental Radiohematology Unit, Centre de Recherches du Service de Santé des Armées, La Tronche, France.
Herodin
F
F
Norol
F
F
Mourcin
F
F
Mayol
J F
JF
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D002453:Cell Cycle; D002478:Cells, Cultured; D005434:Flow Cytometry; D016193:G1 Phase; D016195:G2 Phase; D006098:Granulocytes / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation; D007377:Interleukin-3 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008938:Mitosis; D010215:Papio; D010641:Phenotype; D016192:Resting Phase, Cell Cycle; D019089:Stem Cell Factor / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D013926:Thrombopoietin / Q000378:metabolism*; D013997:Time Factors
D018952:Antigens, CD34; D007377:Interleukin-3; D008565:Membrane Proteins; D019089:Stem Cell Factor; C084881:flt3 ligand protein; D013926:Thrombopoietin