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a Institute of Reproductive and Developmental Biology,
b Department of Haematology, and
c Department of Muscle Cell Biology, Imperial College London, London, United Kingdom
Key Words. Mesenchymal Stem Cells • Lentivirus • Retrovirus • Gene Therapy • Fetal
Correspondence: Jerry Chan, Institute of Reproductive and Developmental Biology & Queen Charlote’s and Chelsea Hospital, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom; Telephone: 44-207-594-2121; Fax: 44-207-594-2154; e-mail j.chan{at}imperial.ac.uk.
First-trimester fetal blood contains a readily expandable population of stem cells, human fetal mesenchymal stem cells (hfMSCs), which might be exploited for autologous intrauterine gene therapy. We investigated the self-renewal and differentiation of hfMSCs after transduction with onco-retroviral and lentiviral vectors. After transduction with either a MoMuLV retrovirus or an HIV-1-based lentiviral vector carrying the ß-galactosidase and green fluorescent reporter gene, respectively, transgene expression, self-renewal, and differentiation capabilities were assessed 2 and 14 weeks later. Transduction with the lentiviral vector resulted in higher efficiencies than with the MoMuLV-based vector (mean, 97.7 ± 1.4% versus 80.2 ± 5.4%; p = .02). Transgene expression was maintained with lentiviral-transduced cells (94.6 ± 2.6%) but decreased over 14 weeks in culture with onco-retroviral-transduced cells (48.3 ± 3.9%). The self-renewal capability of these cells and their ability to undergo osteogenic, adipogenic, and myogenic differentiation was unimpaired after transduction with either vector. Finally, clonal expansion of lentivirally modified cells was expanded over 20 population doublings with maintenance of multiline age differentiation capacity. These results suggest that hfMSCs may be suitable targets for ex vivo genetic manipulation with onco-retroviral or lentiviral vectors without affecting their stem cell properties.
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