Successful reconstitution of human hematopoiesis in the SCID-hu mouse by genetically modified, highly enriched progenitors isolated from fetal liver.
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.
Humeau
L
L
Laboratoire de Biologie Cellulaire, Centre de Thérapie Génique, Institut Paoli-Calmettes, Marseille, France.
Chabannon
C
C
Firpo
M T
MT
Mannoni
P
P
Bagnis
C
C
Roncarolo
M G
MG
Namikawa
R
R
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018920:Coculture Techniques; D005260:Female; D016332:Fetal Tissue Transplantation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000196:embryology; D051379:Mice; D016513:Mice, SCID; D011247:Pregnancy; D012190:Retroviridae