scholarly journals The Late Dividing Population of γ-Retroviral Vector Transduced Human Mobilized Peripheral Blood Progenitor Cells Contributes Most to Gene-Marked Cell Engraftment in Nonobese Diabetic/Severe Combined Immunodeficient Mice

Stem Cells ◽  
2007 ◽  
Vol 25 (7) ◽  
pp. 1807-1813 ◽  
Author(s):  
Sebastian Brenner ◽  
Martin F. Ryser ◽  
Narda L. Whiting-Theobald ◽  
Marcus Gentsch ◽  
Gilda F. Linton ◽  
...  
Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1237-1248 ◽  
Author(s):  
B. Schiedlmeier ◽  
K. Kühlcke ◽  
H. G. Eckert ◽  
C. Baum ◽  
W. J. Zeller ◽  
...  

Mobilized peripheral blood progenitor cells (PBPC) are a potential target for the retrovirus-mediated transfer of cytostatic drug-resistance genes. We analyzed nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse-repopulating CD34+ PBPC from patients with cancer after retroviral transduction in various cytokine combinations with the hybrid vector SF-MDR, which is based on the Friend mink cell focus-forming/murine embryonic stem-cell virus and carries the human multidrug resistance 1 (MDR1) gene. Five to 13 weeks after transplantation of CD34+ PBPC into NOD/SCID mice (n = 84), a cell dose-dependent multilineage engraftment of human leukocytes up to an average of 33% was observed. The SF-MDR provirus was detected in the bone marrow (BM) and in its granulocyte fractions in 96% and 72%, respectively, of chimeric NOD/SCID mice. SF-MDR provirus integration assessed by quantitative real-time polymerase chain reaction (PCR) was optimal in the presence of Flt-3 ligand/thrombopoietin/stem-cell factor, resulting in a 6-fold (24% ± 5% [mean ± SE]) higher average proportion of gene-marked human cells in NOD/SCID mice than that achieved with IL-3 alone (P < .01). A population of clearly rhodamine-123dull human myeloid progeny cells could be isolated from BM samples from chimeric NOD/SCID mice. On the basis of PCR and rhodamine-123 efflux data, up to 18% ± 4% of transduced cells were calculated to express the transgene. Our data suggest that the NOD/SCID model provides a valid assay for estimating the gene-transfer efficiency to repopulating human PBPC that may be achievable in clinical autologous transplantation. P-glycoprotein expression sufficient to prevent marrow aplasia in vivo may be obtained with this SF-MDR vector and an optimized transduction protocol.


1998 ◽  
Vol 21 (6_suppl) ◽  
pp. 1-10
Author(s):  
C. Carlo-Stella ◽  
V. Rizzoli

Mobilized peripheral blood progenitor cells (PBPC) are increasingly used to reconstitute hematopoiesis in patients undergoing high-dose chemoradiotherapy. PBPC collections comprise a heterogeneous population containing both committed progenitors and pluripotent stem cells and can be harvested (i) in steady state, (ii) after chemotherapeutic conditioning, (iii) growth factor priming, or (iv) both. The use of PBPC has opened new therapeutic perspectives mainly related to the availability of large amounts of mobilized hematopoietic stem and progenitor cells. Extensive manipulation of the grafts, including the possibility of exploiting these cells as vehicles for gene therapy strategies, are now possible and will be reviewed.


2000 ◽  
Vol 69 (1) ◽  
pp. 135 ◽  
Author(s):  
Christine Colby ◽  
Qing Chang ◽  
Yasushi Fuchimoto ◽  
Vincent Ferrara ◽  
Michael Murphy ◽  
...  

Stem Cells ◽  
1997 ◽  
Vol 15 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Clara Cesana ◽  
Carmelo Carlo‐Stella ◽  
Lina Mangoni ◽  
Ester Regazzi ◽  
Daniela Garau ◽  
...  

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