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, J M Heard, B Peault, P Lehn

Research output: Contribution to journalArticlepeer-review

Abstract

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 GRIP 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 he transduced into CD34(+) cord blood cells endowed with T-cell differentiation potential, and suggest strategies for T-cell lineage gene therapy in the neonate. (C) 1996 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalBlood
Volume88
Issue number1
Publication statusPublished - 1 Jul 1996

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