Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34+ bone marrow cells, following gamma irradiation in cynomolgus macaques.
BACKGROUND
Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myeloablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques.


RESULTS
The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% +/- 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudotyped and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% +/- 10%). A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producingeGFP were detected as early as three days after transplantation, and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery.


CONCLUSIONS
The transplantation of CD34+ bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T- and B-lymphocyte, thrombocyte and red blood cell compartments.
Derdouch
Sonia
S
CEA, service d'Immuno-Virologie, Institut des Maladies Emergentes et Thérapies Innovantes, Direction des Sciences du Vivant, Fontenay aux Roses, France. sonia.derdouch@necker.fr
Gay
Wilfried
W
Nègre
Didier
D
Prost
Stéphane
S
Le Dantec
Mikael
M
Delache
Benoît
B
Auregan
Gwenaelle
G
Andrieu
Thibault
T
Leplat
Jean-Jacques
JJ
Cosset
François-Loïc
FL
Le Grand
Roger
R
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis / Q000235:genetics; D001854:Bone Marrow Cells / Q000528:radiation effects*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D005720:Gamma Rays; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology*; D008251:Macaca; D008252:Macaca fascicularis; D022423:Myeloid Cells / Q000166:cytology*; D014182:Transplantation, Autologous
D018952:Antigens, CD34