Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 12, Pages 8295-8300Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.122131099
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Funding
- NHLBI NIH HHS [U01 HL066947, HL 66947] Funding Source: Medline
- NIDDK NIH HHS [K08 DK002776, P01 DK 55759, K08 DK 02776-02, R01 DK055759, K08 DK 02980-01, K08 DK002980] Funding Source: Medline
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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.
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