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Extensive amplification and self-renewal of human primitive hematopoietic
stem cells from cord blood
W Piacibello, F Sanavio, L Garetto, A Severino, D Bergandi, J Ferrario, F Fagioli, M Berger and M Aglietta
Department of Biomedical Sciences, Torino Medical School, University of
Torino, Italy.
The use of umbilical cord blood as a source of marrow repopulating cells
for the treatment of pediatric malignancies has been established. Given the
general availability, the ease of procurement, and progenitor content, cord
blood is an attractive alternative to bone marrow or growth factor
mobilized peripheral blood cells as a source of transplantable
hematopoietic tissue. However, there is a major potential limitation to the
widespread use of cord blood as a source of hematopoietic stem cells for
marrow replacement and gene therapy. There may be enough hematopoietic stem
cells to reconstitute children, but the ability to engraft an adult might
require ex vivo manipulations. We describe an in vitro system in which the
growth of cord blood CD34+ cells is sustained and greatly expanded for more
than 6 months by the simple combination of two hematopoietic growth
factors. Progenitors and cells belonging to all hematopoietic lineages are
continuously and increasingly generated (the number of colony-forming
unit-granulocyte- macrophage [CFU-GM] present at the end of 6 months of
culture are well over 2,000,000-fold the CFU-GM present at the beginning of
the culture). Very primitive hematopoietic progenitors, including long-term
culture-initiating cells (LTC-ICs) and blast cell colony-forming units, are
also greatly expanded (after 20 weeks of liquid culture, LTC-IC number is
over 200,000-fold the initial number). The extremely prolonged maintenance
and the massive expansion of these progenitors, which share many
similarities with murine long-term repopulating cells, suggest that
extensive renewal and little differentiation take place. This system might
prove useful in diverse clinical settings involving treatment of grown-up
children and adults with transplantation of normal or genetically
manipulated hematopoietic stem cells.
Volume 89,
Issue 8,
pp. 2644-2653,
04/15/1997
Copyright © 1997 by The American Society of Hematology
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78(4):
836 - 844.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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16(7):
3323 - 3333.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. De Felice, C. Tatarelli, M. G. Mascolo, C. Gregorj, F. Agostini, R. Fiorini, V. Gelmetti, S. Pascale, F. Padula, M. T. Petrucci, et al.
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65(4):
1505 - 1513.
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[Full Text]
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|
|
|
|
|
|
|
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490 - 497.
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[Full Text]
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|
|
|
|
|
|
|
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[Full Text]
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|
|
|
|
|
|
|
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|
|
|
|
|
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103(12):
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|
|
|
|
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103(7):
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
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21(1):
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[Abstract]
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|
|
|
|
|
|
|
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December 15, 2002;
100(13):
4391 - 4400.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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November 15, 2002;
100(10):
3457 - 3469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Linden and K. Kaushansky
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J. Biol. Chem.,
September 13, 2002;
277(38):
35240 - 35247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-A. Kim, Y.-J. Jung, J.-Y. Seoh, S.-Y. Woo, J.-S. Seo, and H.-L. Kim
Gene Expression Profile of Megakaryocytes from Human Cord Blood CD34+ Cells Ex Vivo Expanded by Thrombopoietin
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September 1, 2002;
20(5):
402 - 416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Challier, L. Cocault, R. Berthier, N. Binart, I. Dusanter-Fourt, G. Uzan, and M. Souyri
The cytoplasmic domain of Mpl receptor transduces exclusive signals in embryonic and fetal hematopoietic cells
Blood,
August 28, 2002;
100(6):
2063 - 2070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Grande, M. Montanari, E. Tagliafico, R. Manfredini, T. Z. Marani, M. Siena, E. Tenedini, A. Gallinelli, and S. Ferrari
Physiological levels of 1{alpha}, 25 dihydroxyvitamin D3 induce the monocytic commitment of CD34+ hematopoietic progenitors
J. Leukoc. Biol.,
April 1, 2002;
71(4):
641 - 651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Chen, X. Cui, and N. J. Chao
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Blood,
March 15, 2002;
99(6):
2235 - 2240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Dravid and S.G.A. Rao
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March 1, 2002;
20(2):
183 - 189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Fan, G. Valdimarsdottir, J. Larsson, A. Brun, M. Magnusson, S. E. Jacobsen, P. ten Dijke, and S. Karlsson
Transient Disruption of Autocrine TGF-{beta} Signaling Leads to Enhanced Survival and Proliferation Potential in Single Primitive Human Hemopoietic Progenitor Cells
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January 15, 2002;
168(2):
755 - 762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Eridani
Stem cells for all seasons? Experimental and clinical issues
J R Soc Med,
January 1, 2002;
95(1):
5 - 8.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-H. Kie, W.-I. Yang, M.-K. Lee, T.-J. Kwon, Y.-H. Min, H.-O. Kim, H.-S. Ahn, S.-A. Im, H.-L. Kim, H.-Y. Park, et al.
Decrease in Apoptosis and Increase in Polyploidization of Megakaryocytes by Stem Cell Factor During Ex Vivo Expansion of Human Cord Blood CD34+ Cells Using Thrombopoietin
Stem Cells,
January 1, 2002;
20(1):
73 - 79.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. Wu, S. L. Smith, and M. E. Dolan
High Efficiency Electroporation of Human Umbilical Cord Blood CD34+ Hematopoietic Precursor Cells
Stem Cells,
November 1, 2001;
19(6):
492 - 499.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
Y. J. Summers, C. M. Heyworth, E. A. de Wynter, J. Chang, and N. G. Testa
Cord Blood G0 CD34+ Cells Have A Thousand-Fold Higher Capacity For Generating Progenitors In Vitro Than G1 CD34+ Cells
Stem Cells,
November 1, 2001;
19(6):
505 - 513.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. Ro{beta}manith, B. Schroder, G. Bug, P. Muller, T. Klenner, R. Knaus, D. Hoelzer, and O.G. Ottmann
Interleukin 3 Improves the Ex Vivo Expansion of Primitive Human Cord Blood Progenitor Cells and Maintains the Engraftment Potential of SCID Repopulating Cells
Stem Cells,
July 1, 2001;
19(4):
313 - 320.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. D. Lewis, G. Almeida-Porada, J. Du, I. R. Lemischka, K. A. Moore, E. D. Zanjani, and C. M. Verfaillie
Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system
Blood,
June 1, 2001;
97(11):
3441 - 3449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Debili, C. Robin, V. Schiavon, R. Letestu, F. Pflumio, M.-T. Mitjavila-Garcia, L. Coulombel, and W. Vainchenker
Different expression of CD41 on human lymphoid and myeloid progenitors from adults and neonates
Blood,
April 1, 2001;
97(7):
2023 - 2030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. S. Rosler, J. E. Brandt, J. Chute, and R. Hoffman
An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells
Blood,
November 15, 2000;
96(10):
3414 - 3421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Matsumoto, K. Yasui, N. Yamashita, Y. Horie, T. Yamada, Y. Tani, H. Shibata, and T. Nakano
In Vitro Proliferation Potential of AC133 Positive Cells in Peripheral Blood
Stem Cells,
May 1, 2000;
18(3):
196 - 203.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. J. Szilvassy, T. E. Meyerrose, and B. Grimes
Effects of cell cycle activation on the short-term engraftment properties of ex vivo expanded murine hematopoietic cells
Blood,
May 1, 2000;
95(9):
2829 - 2837.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. K. Shadduck, G. L. Gilmore, and J. Lister
Role of Serum-Free Medium in the Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells
Stem Cells,
March 1, 2000;
18(2):
154 - 155.
[Full Text]
|
|
|
|
|
|
|
J.-J. Lataillade, D. Clay, C. Dupuy, S. Rigal, C. Jasmin, P. Bourin, and M.-C. L. Bousse-Kerdiles
Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival
Blood,
February 1, 2000;
95(3):
756 - 768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Crapnell, E. D. Zanjani, A. Chaudhuri, J. L. Ascensao, S. St. Jeor, and J. P. Maciejewski
In vitro infection of megakaryocytes and their precursors by human cytomegalovirus
Blood,
January 15, 2000;
95(2):
487 - 493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
