1. 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.
- Author
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Derdouch, Sonia, Gay, Wilfried, Nègre, Didier, Prost, Stéphane, Le Dantec, Mikael, Delache, Benoît, Auregan, Gwenaelle, Andrieu, Thibault, Leplat, Jean-Jacques, Cosset, François-Loïc, and Le Grand, Roger
- Subjects
BONE marrow cells ,STEM cell transplantation ,BLOOD cells ,BLOOD platelets ,ERYTHROCYTES - Abstract
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. Conclusion: 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 Blymphocyte, thrombocyte and red blood cell compartments. [ABSTRACT FROM AUTHOR]- Published
- 2008
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