%0 Journal Article
%T 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
%A Sonia Derdouch
%A Wilfried Gay
%A Didier N¨¨gre
%A St¨¦phane Prost
%A Mikael Le Dantec
%A Beno£¿t Delache
%A Gwenaelle Auregan
%A Thibault Andrieu
%A Jean-Jacques Leplat
%A Fran£¿ois-Lo£¿c Cosset
%A Roger Le Grand
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-50
%X The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% ¡À 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% ¡À 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.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.Gene therapy strategies hold promise for the treatment of hematopoietic disorders. All hematopoietic lineages, including polymorphonuclear cells, monocytes, lymphocytes and natural killer cells, and hematopoietic stem cells (HSC) ¨C which are capable of self-renewal and pluripotent differentiation ¨C have been targeted for transduction with therapeutic genes. Most diseases for which gene therapy could be proposed require stable and long-lasting transgene expression for efficacy. Retroviral vectors present the major advantage of integrating the transferred DNA stably into the genome of target cells, which is then passed on to progeny. However, they cannot infect and integrate into non dividing cells[1]. Most HSC are quiescent [2], respond slowly to stimulation [3-7] and tend to differentiate and lose their repopulating capacity upon stimulation[3,8-11]. Lentiviral vectors can be used
%U http://www.retrovirology.com/content/5/1/50