|
|
 Previous Article | Table of Contents | Next Article 
Efficient Retroviral-Mediated Gene Transfer to Human Cord Blood Stem
Cells With In Vivo Repopulating Potential
E. Conneally,
C.J. Eaves, and
R.K. Humphries
From the Terry Fox Laboratory; BC Cancer Agency; and the Departments
of Pathology and Laboratory Medicine, Medical Genetics, and Medicine of
the University of British Columbia, Vancouver, BC, Canada.
Recent studies have shown efficient gene transfer to primitive
progenitors in human cord blood (CB) when the cells are incubated in
retrovirus-containing supernatants on fibronectin-coated dishes. We
have now used this approach to achieve efficient gene transfer to human
CB cells with the capacity to regenerate lymphoid and myeloid progeny
in nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. CD34+ cell-enriched populations
were first cultured for 3 days in serum-free medium containing
interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor,
Flt3-ligand, and Steel factor followed by two 24-hour incubations with
a MSCV-NEO virus-containing medium obtained under either
serum-free or serum-replete conditions. The presence of serum during
the latter 2 days made no consistent difference to the total number of
cells, colony-forming cells (CFC), or long-term culture-initiating
cells (LTC-IC) recovered at the end of the 5-day culture period, and
the cells infected under either condition regenerated similar numbers
of human CD34+ (myeloid) CFC and human
CD19+ (B lymphoid) cells for up to 20 weeks in NOD/SCID
recipients. However, the presence of serum increased the viral titer in
the producer cell-conditioned medium and this was correlated with a
twofold to threefold higher efficiency of gene transfer to all progenitor types. With the higher titer viral supernatant, 17% ± 3%
and 17% ± 8%, G418-resistant in vivo repopulating cells and LTC-IC
were obtained. As expected, the proportion of NEO + repopulating cells determined by polymerase chain reaction analysis of in vivo generated CFC was even higher (32% ± 10%). There was no correlation between the frequency of gene transfer to LTC-IC and colony-forming unit-granulocyte-macrophage (CFU-GM), or to NOD/SCID repopulating cells and CFU-GM (r2 = 0.16 and 0.17, respectively),
whereas values for LTC-IC and NOD/SCID repopulating cells were highly
and significantly correlated (r2 = 0.85). These findings
provide further evidence of a close relationship between human LTC-IC
and NOD/SCID repopulating cells (assessed using a  6-week CFC output
endpoint) and indicate the predictive value of gene transfer
measurements to such LTC-IC for the design of clinical gene therapy
protocols.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3487-3493
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Gonzalez-Murillo, M. L. Lozano, E. Montini, J. A. Bueren, and G. Guenechea
Unaltered repopulation properties of mouse hematopoietic stem cells transduced with lentiviral vectors
Blood,
October 15, 2008;
112(8):
3138 - 3147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. R. Santoni de Sio, P. Cascio, A. Zingale, M. Gasparini, and L. Naldini
Proteasome activity restricts lentiviral gene transfer into hematopoietic stem cells and is down-regulated by cytokines that enhance transduction
Blood,
June 1, 2006;
107(11):
4257 - 4265.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Schiedlmeier, H. Klump, E. Will, G. Arman-Kalcek, Z. Li, Z. Wang, A. Rimek, J. Friel, C. Baum, and W. Ostertag
High-level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage on human cord blood CD34+ cells, but impairs lymphomyeloid differentiation
Blood,
March 1, 2003;
101(5):
1759 - 1768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. E. Nicolini, S. Imren, I.-H. Oh, R. K. Humphries, P. Leboulch, M. E. Fabry, R. L. Nagel, and C. J. Eaves
Expression of a human beta -globin transgene in erythroid cells derived from retrovirally transduced transplantable human fetal liver and cord blood cells
Blood,
July 30, 2002;
100(4):
1257 - 1264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lei, B. Bajaj, and S. T. Andreadis
Retrovirus-Associated Heparan Sulfate Mediates Immobilization and Gene Transfer on Recombinant Fibronectin
J. Virol.,
July 29, 2002;
76(17):
8722 - 8728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Tsai, H. L. Malech, M. R. Kirby, A. P. Hsu, N. E. Seidel, C. D. Porada, E. D. Zanjani, D. M. Bodine, and J. M. Puck
Retroviral transduction of IL2RG into CD34+ cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras
Blood,
June 17, 2002;
100(1):
72 - 79.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. An, S. K. P. Kung, A. Bonifacino, R. P. Wersto, M. E. Metzger, B. A. Agricola, S. H. Mao, I. S. Y. Chen, and R. E. Donahue
Lentivirus Vector-Mediated Hematopoietic Stem Cell Gene Transfer of Common Gamma-Chain Cytokine Receptor in Rhesus Macaques
J. Virol.,
April 15, 2001;
75(8):
3547 - 3555.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. Rovira, M. De Angioletti, O. Camacho-Vanegas, D. Liu, V. Rosti, H. F. Gallardo, R. Notaro, M. Sadelain, and L. Luzzatto
Stable in vivo expression of glucose-6-phosphate dehydrogenase (G6PD) and rescue of G6PD deficiency in stem cells by gene transfer
Blood,
December 15, 2000;
96(13):
4111 - 4117.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Maguer-Satta, R. Oostendorp, D. Reid, and C. J. Eaves
Evidence that ceramide mediates the ability of tumor necrosis factor to modulate primitive human hematopoietic cell fates
Blood,
December 15, 2000;
96(13):
4118 - 4123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Glimm, I.-H. Oh, and C. J. Eaves
Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0
Blood,
December 15, 2000;
96(13):
4185 - 4193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Cashman and C. J. Eaves
High marrow seeding efficiency of human lymphomyeloid repopulating cells in irradiated NOD/SCID mice
Blood,
December 1, 2000;
96(12):
3979 - 3981.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Barrette, J. L. Douglas, N. E. Seidel, and D. M. Bodine
Lentivirus-based vectors transduce mouse hematopoietic stem cells with similar efficiency to Moloney murine leukemia virus-based vectors
Blood,
November 15, 2000;
96(10):
3385 - 3391.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Hennemann, I.-H. Oh, J. Y. Chuo, C. P. Kalberer, P. D. Schley, S. Rose-John, R. K. Humphries, and C. J. Eaves
Efficient retrovirus-mediated gene transfer to transplantable human bone marrow cells in the absence of fibronectin
Blood,
October 1, 2000;
96(7):
2432 - 2439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Crooks, Q.-L. Hao, D. Petersen, L. W. Barsky, and D. Bockstoce
IL-3 Increases Production of B Lymphoid Progenitors from Human CD34+CD38- Cells
J. Immunol.,
September 1, 2000;
165(5):
2382 - 2389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Bryder and S. E. W. Jacobsen
Interleukin-3 supports expansion of long-term multilineage repopulating activity after multiple stem cell divisions in vitro
Blood,
September 1, 2000;
96(5):
1748 - 1755.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. F. Kelly, J. Vandergriff, A. Nathwani, A. W. Nienhuis, and E. F. Vanin
Highly efficient gene transfer into cord blood nonobese diabetic/severe combined immunodeficiency repopulating cells by oncoretroviral vector particles pseudotyped with the feline endogenous retrovirus (RD114) envelope protein
Blood,
August 15, 2000;
96(4):
1206 - 1214.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. F. Srour;, C. Eaves, and H. Glimm
Proliferative history and hematopoietic function of ex vivo expanded human CD34+ cells
Blood,
August 15, 2000;
96(4):
1609 - 1612.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. MacKenzie, N. R. Hackett, R. G. Crystal, and M. A. S. Moore
Adenoviral vector-mediated gene transfer to primitive human hematopoietic progenitor cells: assessment of transduction and toxicity in long-term culture
Blood,
July 1, 2000;
96(1):
100 - 108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Barquinero, J. C. Segovia, M. Ramirez, A. Limon, G. Guenechea, T. Puig, J. Briones, J. Garcia, and J. A. Bueren
Efficient transduction of human hematopoietic repopulating cells generating stable engraftment of transgene-expressing cells in NOD/SCID mice
Blood,
May 15, 2000;
95(10):
3085 - 3093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Schiedlmeier, K. Kuhlcke, H. G. Eckert, C. Baum, W. J. Zeller, and S. Fruehauf
Quantitative assessment of retroviral transfer of the human multidrug resistance 1 gene to human mobilized peripheral blood progenitor cells engrafted in nonobese diabetic/severe combined immunodeficient mice
Blood,
February 15, 2000;
95(4):
1237 - 1248.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Donahue, R. P. Wersto, J. A. Allay, B. A. Agricola, M. E. Metzger, A. W. Nienhuis, D. A. Persons, and B. P. Sorrentino
High levels of lymphoid expression of enhanced green fluorescent protein in nonhuman primates transplanted with cytokine-mobilized peripheral blood CD34+ cells
Blood,
January 15, 2000;
95(2):
445 - 452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Williams, A. W. Nienhuis, R. G. Hawley, and F. O. Smith
Gene Therapy 2000
Hematology,
January 1, 2000;
2000(1):
376 - 393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dorrell, O. I. Gan, D. S. Pereira, R. G. Hawley, and J. E. Dick
Expansion of human cord blood CD34+CD38- cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function
Blood,
January 1, 2000;
95(1):
102 - 110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Glimm and C.J. Eaves
Direct Evidence for Multiple Self-Renewal Divisions of Human In Vivo Repopulating Hematopoietic Cells in Short-Term Culture
Blood,
October 1, 1999;
94(7):
2161 - 2168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. D. Zanjani and W. F. Anderson
Prospects for in Utero Human Gene Therapy
Science,
September 24, 1999;
285(5436):
2084 - 2088.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
L. E. Ailles, B. Gerhard, H. Kawagoe, and D. E. Hogge
Growth Characteristics of Acute Myelogenous Leukemia Progenitors That Initiate Malignant Hematopoiesis in Nonobese Diabetic/Severe Combined Immunodeficient Mice
Blood,
September 1, 1999;
94(5):
1761 - 1772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Dinauer, L. L. Li, H. Bjorgvinsdottir, C. Ding, and N. Pech
Long-Term Correction of Phagocyte NADPH Oxidase Activity by Retroviral-Mediated Gene Transfer in Murine X-Linked Chronic Granulomatous Disease
Blood,
August 1, 1999;
94(3):
914 - 922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Robin, F. Pflumio, W. Vainchenker, and L. Coulombel
Identification of Lymphomyeloid Primitive Progenitor Cells in Fresh Human Cord Blood and in the Marrow of Nonobese Diabetic-Severe Combined Immunodeficient (NOD-SCID) Mice Transplanted with Human CD34+ Cord Blood Cells
J. Exp. Med.,
May 17, 1999;
189(10):
1601 - 1610.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. MacNeill, H. Hanenberg, K. E. Pollok, J. C. M. van der Loo, M. F. A. Bierhuizen, G. Wagemaker, and D. A. Williams
Simultaneous Infection with Retroviruses Pseudotyped with Different Envelope Proteins Bypasses Viral Receptor Interference Associated with Colocalization of gp70 and Target Cells on Fibronectin CH-296
J. Virol.,
May 1, 1999;
73(5):
3960 - 3967.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
V. I. Rebel, M. Tanaka, J.-S. Lee, S. Hartnett, M. Pulsipher, D. G. Nathan, R. C. Mulligan, and C. A. Sieff
One-Day Ex Vivo Culture Allows Effective Gene Transfer Into Human Nonobese Diabetic/Severe Combined Immune-Deficient Repopulating Cells Using High-Titer Vesicular Stomatitis Virus G Protein Pseudotyped Retrovirus
Blood,
April 1, 1999;
93(7):
2217 - 2224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Guenechea, J.C. Segovia, B. Albella, M. Lamana, M. Ramirez, C. Regidor, M.N. Fernandez, and J.A. Bueren
Delayed Engraftment of Nonobese Diabetic/Severe Combined Immunodeficient Mice Transplanted With Ex Vivo-Expanded Human CD34+ Cord Blood Cells
Blood,
February 1, 1999;
93(3):
1097 - 1105.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Miyoshi, K. A. Smith, D. E. Mosier, I. M. Verma, and B. E. Torbett
Transduction of Human CD34+ Cells That Mediate Long-Term Engraftment of NOD/SCID Mice by HIV Vectors
Science,
January 29, 1999;
283(5402):
682 - 686.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. D. Cashman and C. J. Eaves
Human Growth Factor-Enhanced Regeneration of Transplantable Human Hematopoietic Stem Cells in Nonobese Diabetic/Severe Combined Immunodeficient Mice
Blood,
January 15, 1999;
93(2):
481 - 487.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. B. van Hennik, M. M.A. Verstegen, M. F.A. Bierhuizen, A. Limon, A. W. Wognum, J. A. Cancelas, J. Barquinero, R. E. Ploemacher, and G. Wagemaker
Highly Efficient Transduction of the Green Fluorescent Protein Gene in Human Umbilical Cord Blood Stem Cells Capable of Cobblestone Formation in Long-Term Cultures and Multilineage Engraftment of Immunodeficient Mice
Blood,
December 1, 1998;
92(11):
4013 - 4022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. Frankel, M. Lilly, R. Kreitman, D. Hogge, M. Beran, M. H. Freedman, P. D. Emanuel, C. McLain, P. Hall, E. Tagge, et al.
Diphtheria Toxin Fused to Granulocyte-Macrophage Colony-Stimulating Factor Is Toxic to Blasts From Patients With Juvenile Myelomonocytic Leukemia and Chronic Myelomonocytic Leukemia
Blood,
December 1, 1998;
92(11):
4279 - 4286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
