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A cell surface marker gene transferred with a retroviral vector into CD34+
cord blood cells is expressed by their T-cell progeny in the SCID- hu
thymus
C Champseix, V Marechal, I Khazaal, O Schwartz, S Fournier, N Schlegel, G Dranoff, O Danos, P Blot, E Vilmer, JM Heard, B Peault and P Lehn
Institut d'Embryologie Cellulaire et Moleculaire du CNRS et du College de
France, Nogent-sur-Marne, France.
Gene transduction into immature hematopoietic cells collected at birth from
the umbilical cord could be useful for the treatment of genetic or acquired
disorders of the hematopoietic system diagnosed during pregnancy. The
SCID-hu mouse is a convenient model to investigate T- cell lineage gene
therapy, since it allows replication of human intrathymic T-cell
development. CD34+ cells isolated from cord blood were cocultured with CRIP
MFG-murine CD2 (mCD2) cells that produce recombinant retroviruses encoding
the mCD2 antigen, a cell surface marker easily detectable by flow
cytometry. After 3 and 4 days in coculture, a mean of 19% and 39% human
hematopoietic cells, respectively, expressed the mCD2 antigen. CD34+ cells
cocultured for 4 days were used to reconstitute human fetal thymus
implanted in SCID mice. Five to 10 weeks later, the mCD2 antigen was
detected on approximately 10% of human thymocytes repopulating the thymic
grafts in four of nine SCID mouse chimeras. Vector genomes were detected in
graft cell DNA by Southern blot. Analysis of vector integration indicated
that positive cells were of polyclonal origin in three animals and
predominantly monoclonal in the other one. Our data show that foreign genes
can be transduced into CD34+ cord blood cells endowed with T-cell
differentiation potential, and suggest strategies for T-cell lineage gene
therapy in the neonate.
Volume 88,
Issue 1,
pp. 107-113,
07/01/1996
Copyright © 1996 by The American Society of Hematology
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