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Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34 super(+ )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 transpla...

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Published in:Retrovirology 2008-01, Vol.5, p.50-50
Main Authors: Derdouch, Sonia, Gay, Wilfried, Negre, Didier, Prost, Stephane, Le Dantec, Mikael, Delache, Benoit, Auregan, Gwenaelle, Andrieu, Thibault, Leplat, Jean-Jacques, Cosset, Francois-Loic, Le Grand, Roger
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Language:English
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Summary: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 super(+ )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% c 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% c 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 super(+ )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.
ISSN:1742-4690
1742-4690
DOI:10.1186/1742-4690-5-50