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

• Published in: Retrovirology 2008-06, Vol.5 (1), p.50-50, Article 50
• Main Authors: Derdouch, Sonia, Gay, Wilfried, Nègre, Didier, Prost, Stéphane, Le Dantec, Mikael, Delache, Benoît, Auregan, Gwenaelle, Andrieu, Thibault, Leplat, Jean-Jacques, Cosset, François-Loïc, Le Grand, Roger
• Format: Article
• Language: English
• Subjects: Animal genetics; Animals; Antigens, CD34 - analysis; Antigens, CD34 - genetics; Bone Marrow Cells - radiation effects; Bone Marrow Transplantation; Cell Differentiation; Gamma Rays; Genetics; Hematopoietic Stem Cells - metabolism; Life Sciences; Lymphocytes - cytology; Macaca; Macaca fascicularis; Myeloid Cells - cytology; Transplantation, Autologous
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/1742-4690-5-50

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. 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. 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.