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Successful Reconstitution of Human Hematopoiesis in the SCID-hu Mouse by Genetically Modified, Highly Enriched Progenitors Isolated From Fetal Liver

Laurent Humeau, Christian Chabannon, Meri T. Firpo, Patrice Mannoni, Claude Bagnis, Maria-Grazia Roncarolo, and Reiko Namikawa

From the Laboratoire de Biologie Cellulaire, Centre de Thérapie Génique, Institut Paoli-Calmettes, Marseille, France; and the Human Immunology Department, DNAX Research Institute of Molecular and Cellular Biology, Inc, Palo Alto, CA.

Highly purified CD34++CD38-Lin- hematopoietic progenitors isolated from human fetal liver were infected with the murine retroviral vector, MFG nls-LacZ, which encodes a modified version of the Escherichia coli beta -galactosidase gene. Progenitors that were cocultured with the packaging cell line could reconstitute human bone marrow or thymus implanted in SCID-hu mice. Expression of the beta -galactosidase gene was observed in primitive and committed clonogenic progenitors, mature myeloid, B-lineage cells, and T-lineage cells for up to 4 months after injection into SCID-hu mice. Furthermore, hematopoietic reconstitution by genetically modified progenitor cells could be achieved by the injection of the cells generated from as few as 500 CD34++CD38-Lin- cells, suggesting efficient retroviral gene transfer into fetal liver progenitors.

Blood, Vol. 90 No. 9 (November 1), 1997: pp. 3496-3506
© 1997 by The American Society of Hematology.


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