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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 Tranplantability

^a Centre de Recherches du Service de Santé des Armées, La Tronche, France;
^b Unité de Thérapie cellulaire, Service d'Hématologie Clinique, Groupe Hospitalier Pitié Salpétrière, Paris, France

Key Words. CD34⁺ cells • Bone marrow aplasia • Cell cycle • Nonhuman primate • Cytokines • Ex vivo expansion

Correspondence: M. Drouet, M.D., Ph.D., Experimental Radiohematology Unit, Centre de Recherches du Service de Santé des Armées, 24 avenue des Maquis du Grésivaudan BP 87-38702 La Tronche Cedex, France; Telephone 33-4-76-63-69-28.

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.