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Titolo:
Stable transduction with lentiviral vectors and amplification of immature hematopoietic progenitors from cord blood of preterm human fetuses
Autore:
Luther-Wyrsch, A; Costello, E; Thali, M; Buetti, E; Nissen, C; Surbek, D; Holzgreve, W; Gratwohl, A; Tichelli, A; Wodnar-Filipowicz, A;
Indirizzi:
Univ Basel Hosp, Dept Res, Lab Expt Hematol, CH-4031 Basel, Switzerland Univ Basel Hosp Basel Switzerland CH-4031 ol, CH-4031 Basel, Switzerland Univ Lausanne, Inst Microbiol, Lausanne, Switzerland Univ Lausanne Lausanne Switzerland nst Microbiol, Lausanne, Switzerland Univ Basel Hosp, Dept Obstet & Gynecol, CH-4031 Basel, Switzerland Univ Basel Hosp Basel Switzerland CH-4031 ol, CH-4031 Basel, Switzerland Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland Univ Basel HospBasel Switzerland CH-4031 ol, CH-4031 Basel, Switzerland
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 4, volume: 12, anno: 2001,
pagine: 377 - 389
SICI:
1043-0342(200103)12:4<377:STWLVA>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
SEVERE COMBINED IMMUNODEFICIENCY; IN-UTERO TRANSPLANTATION; MURINE LEUKEMIA-VIRUS; HUMAN CD34(+) CELLS; VIVO GENE DELIVERY; BONE-MARROW CELLS; STEM-CELLS; SELF-RENEWAL; UNRELATED DONORS; T-LYMPHOCYTES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Wodnar-Filipowicz, A Univ Basel Hosp, Dept Res, Lab Expt Hematol, Hebelstr20, CH-4031 Basel, Switzerland Univ Basel Hosp Hebelstr 20 Basel Switzerland CH-4031
Citazione:
A. Luther-Wyrsch et al., "Stable transduction with lentiviral vectors and amplification of immature hematopoietic progenitors from cord blood of preterm human fetuses", HUM GENE TH, 12(4), 2001, pp. 377-389

Abstract

Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34(+) cells from CB at weeks24 to 34 of pregnancy, using lentiviral vector-mediated transfer of the green fluorescent protein (GFP) gene. The transduction rate of CD34(+) cells was 42 +/- 9%, resulting in GFP expression in 23 +/- 4% of colonies derivedfrom colony-forming units (CFUs) and 11 +/- 1% from primitive long-term culture-initiating cells (LTC-ICs). Cell cycle analysis demonstrated transduction and GFP expression in cells in the G(0) phase, which contains immaturehematopoietic progenitors. Transduced fetal CD34(+) cells could be expanded 1000-fold in long-term cultures supplemented with megakaryocyte growth and development factor along with Flt-3 ligand. At week 10, expression of GFPwas observed in 40.5 +/- 11.7% of CFU-derived colonies. While prestimulation of CD34(+) cells with cytokines prior to transduction increased the efficiency of GFP transfer 2- to 3-fold, long-term maintenance of GFP-expressing CFUs occurred only in the absence of prestimulation. The GFP gene was found integrated into the genomic DNA of 35% of LTC-IC-derived colonies initiated at week 10, but GFP expression was not detectable, suggesting downregulation of transgene activity during the extended culture period. These results indicate that human fetal CB progenitors are amenable to genetic modification by lentiviral vectors and may serve as a target for gene therapy of hematopoietic disorders by prenatal autologous transplantation.

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Documento generato il 05/04/20 alle ore 07:13:50