SUCCESSFUL RECONSTITUTION OF HUMAN HEMATOPOIESIS IN THE SCID-HU MOUSEBY GENETICALLY-MODIFIED, HIGHLY ENRICHED PROGENITORS ISOLATED FROM FETAL LIVER

Highly purified CD34(++)CD38(-)Lin(-) hematopoietic progenitors isolat ed from human fetal liver were infected with the murine retroviral vec tor, MFG nls-LacZ, which encodes a modified version of the Escherichia coli beta-galactosidase gene, Progenitors that were cocultured with t he packaging cell line could reconstitute human bone marrow or thymus implanted in SCID-hu mice, Expression of the beta-galactosidase gene w as 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 reconstitutio n by genetically modified progenitor cells could be achieved by the in jection of the cells generated from as few as 500 CD34(++)CD38(-)Lin(- ) cells, suggesting efficient retroviral gene transfer into fetal live r progenitors, (C) 1997 by The American Society of Hematology.