Transduction of Human NOD/SCID-Repopulating Cells with Both Lymphoid and Myeloid Potential by Foamy Virus Vectors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 12; pp. 8295 - 8300
• Main Authors: Josephson, Neil C., Vassilopoulos, George, Trobridge, Grant D., Priestley, Greg V., Wood, Brent L., Papayannopoulou, Thalia, Russell, David W.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 11.06.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: Animals; Antigens, CD - blood; Antigens, CD19 - blood; B lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Biological Sciences; Blood Transfusion; Bone Marrow Cells - cytology; CD4 Antigens - blood; Cell lines; Cells; Colony-Forming Units Assay; Erythropoietin - pharmacology; Genetic Vectors; Green Fluorescent Proteins; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - virology; Humans; Immunophenotyping; Infant, Newborn; Luminescent Proteins - genetics; Medical research; Membrane Proteins - pharmacology; Mice; Mice, Inbred NOD; Mice, SCID; Myeloid cells; Pluripotent stem cells; Proviruses; Rodents; Spumavirus - genetics; Stem Cell Factor - pharmacology; Stem cell transplantation; Stem cells; Transplantation, Heterologous; Umbilical Cord; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.122131099

The efficiency of gene transfer into human hematopoietic stem cells by oncoretroviral vectors is too low for effective gene therapy of most hematologic diseases. Retroviral vectors based on the nonpathogenic foamy viruses (FV) are an alternative gene-transfer system. In this study, human umbilical cord blood CD34+cells were transduced with FV vectors by a single 10-h exposure to vector stocks and then injected into sublethally irradiated nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice. At 5-7 weeks after transplantation, high transgene expression rates were observed in engrafted human hematopoietic cells, including over 60% of clonogenic progenitors. Significant transgene silencing did not occur. We developed an approach for expanding human cell populations derived from transplanted mice to show that multiple SCID repopulating cells (SRCs) had been transduced, including some that were capable of both lymphoid and myeloid differentiation. These findings demonstrate for the first time that human pluripotent (lympho-myeloid) hematopoietic stem cells repopulate NOD/SCID mice and can be efficiently transduced by FV vectors.