Open AccessCell 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 G 0 /G 1 and S/G 2 /M Graft Cell Content Does Not Correlate with Tranplantability
Author(s) -
Drouet M.,
Herodin F.,
Norol F.,
Mourcin F.,
Mayol J. F.
Publication year - 2001
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.19-5-436
Subject(s) - biology , stem cell factor , stem cell , progenitor cell , haematopoiesis , microbiology and biotechnology , ex vivo , immunology , endothelial stem cell , cd34 , hematopoietic stem cell , transplantation , cancer research , medicine , in vivo , biochemistry , genetics , in vitro
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 G 1 and S/G 2 /M cell amplification (G 0 : 6.1% ± 2.8%; G 0 /G 1 : 64.2% ± 7.2%; S/G 2 /M: 30.4% ± 7.3% respectively of expanded CD34 + cells on average) resulted in the acceleration of short‐term granulocyte recovery. By contrast, G 0 /G 1 and S/G 2 /M cell content of expanded grafts did not correlate with short‐ or long‐term engraftment.