|
|
 Previous Article | Table of Contents | Next Article 
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
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Tesio, L. Gammaitoni, M. Gunetti, V. Leuci, Y. Pignochino, N. Jordaney, S. Capellero, C. Cammarata, L. Caione, G. Migliaretti, et al.
Sustained Long-Term Engraftment and Transgene Expression of Peripheral Blood CD34+ Cells Transduced with Third-Generation Lentiviral Vectors
Stem Cells,
June 1, 2008;
26(6):
1620 - 1627.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Abdel-Azim, Y. Zhu, R. Hollis, X. Wang, S. Ge, Q.-L. Hao, G. Smbatyan, D. B. Kohn, M. Rosol, and G. M. Crooks
Expansion of multipotent and lymphoid-committed human progenitors through intracellular dimerization of Mpl
Blood,
April 15, 2008;
111(8):
4064 - 4074.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D Mrugala, C Bony, N Neves, L Caillot, S Fabre, D Moukoko, C Jorgensen, and D Noel
Phenotypic and functional characterisation of ovine mesenchymal stem cells: application to a cartilage defect model
Ann Rheum Dis,
March 1, 2008;
67(3):
288 - 295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gammaitoni, S. Lucchi, S. Bruno, M. Tesio, M. Gunetti, Y. Pignochino, G. Migliardi, L. Lazzari, M. Aglietta, P. Rebulla, et al.
Serial Transplantations in Nonobese Diabetic/Severe Combined Immunodeficiency Mice of Transduced Human CD34+ Cord Blood Cells: Efficient Oncoretroviral Gene Transfer and Ex Vivo Expansion Under Serum-Free Conditions
Stem Cells,
May 1, 2006;
24(5):
1201 - 1212.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Kindler
Postnatal stem cell survival: does the niche, a rare harbor where to resist the ebb tide of differentiation, also provide lineage-specific instructions?
J. Leukoc. Biol.,
October 1, 2005;
78(4):
836 - 844.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Rookmaaker, M. C. Verhaar, C. J.M. Loomans, R. Verloop, E. Peters, P. E. Westerweel, T. Murohara, F. J.T. Staal, A. J. van Zonneveld, P. Koolwijk, et al.
CD34+ Cells Home, Proliferate, and Participate in Capillary Formation, and in Combination With CD34- Cells Enhance Tube Formation in a 3-Dimensional Matrix
Arterioscler. Thromb. Vasc. Biol.,
September 1, 2005;
25(9):
1843 - 1850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. M. Deasy, B. M. Gharaibeh, J. B. Pollett, M. M. Jones, M. A. Lucas, Y. Kanda, and J. Huard
Long-Term Self-Renewal of Postnatal Muscle-derived Stem Cells
Mol. Biol. Cell,
July 1, 2005;
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.
Histone Deacetylase Inhibitor Valproic Acid Enhances the Cytokine-Induced Expansion of Human Hematopoietic Stem Cells
Cancer Res.,
February 15, 2005;
65(4):
1505 - 1513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Perissinotto, G. Cavalloni, F. Leone, V. Fonsato, S. Mitola, G. Grignani, N. Surrenti, D. Sangiolo, F. Bussolino, W. Piacibello, et al.
Involvement of Chemokine Receptor 4/Stromal Cell-Derived Factor 1 System during Osteosarcoma Tumor Progression
Clin. Cancer Res.,
January 15, 2005;
11(2):
490 - 497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Bella, S. Nicola, I. Timofeeva, M. L. Villa, A. Santoro, and A. C. Berardi
Are interleukin-16 and thrombopoietin new tools for the in vitro generation of dendritic cells?
Blood,
December 15, 2004;
104(13):
4020 - 4028.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. J. Summers, C. M. Heyworth, E. A. de Wynter, C. A. Hart, J. Chang, and N. G. Testa
AC133+ G0 Cells from Cord Blood Show a High Incidence of Long-Term Culture-Initiating Cells and a Capacity for More Than 100 Million-Fold Amplification of Colony-Forming Cells In Vitro
Stem Cells,
September 1, 2004;
22(5):
704 - 715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gammaitoni, K. C. Weisel, M. Gunetti, K.-D. Wu, S. Bruno, S. Pinelli, A. Bonati, M. Aglietta, M. A. S. Moore, and W. Piacibello
Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication
Blood,
June 15, 2004;
103(12):
4440 - 4448.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Chen, S. Antonenko, J. M. Sederstrom, X. Liang, A. S. H. Chan, H. Kanzler, B. Blom, B. R. Blazar, and Y.-J. Liu
Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors
Blood,
April 1, 2004;
103(7):
2547 - 2553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bruno, M. Gunetti, L. Gammaitoni, E. Perissinotto, L. Caione, F. Sanavio, F. Fagioli, M. Aglietta, and W. Piacibello
Fast But Durable Megakaryocyte Repopulation and Platelet Production in NOD/SCID Mice Transplanted with Ex-Vivo Expanded Human Cord Blood CD34+ Cells
Stem Cells,
March 1, 2004;
22(2):
135 - 143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Mulloy, J. Cammenga, F. J. Berguido, K. Wu, P. Zhou, R. L. Comenzo, S. Jhanwar, M. A. S. Moore, and S. D. Nimer
Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element
Blood,
December 15, 2003;
102(13):
4369 - 4376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Leone, E. Perissinotto, G. Cavalloni, V. Fonsato, S. Bruno, N. Surrenti, D. Hong, A. Capaldi, M. Geuna, W. Piacibello, et al.
Expression of the c-ErbB-2/HER2 proto-oncogene in normal hematopoietic cells
J. Leukoc. Biol.,
October 1, 2003;
74(4):
593 - 601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Sitnicka, N. Buza-Vidas, S. Larsson, J. M. Nygren, K. Liuba, and S. E. W. Jacobsen
Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells
Blood,
August 1, 2003;
102(3):
881 - 886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. E. Broxmeyer, E. F. Srour, G. Hangoc, S. Cooper, S. A. Anderson, and D. M. Bodine
High-efficiency recovery of functional hematopoietic progenitor and stem cells from human cord blood cryopreserved for 15 years
PNAS,
January 21, 2003;
100(2):
645 - 650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Balducci, G. Azzarello, M. T. Valenti, G. M. Capuzzo, G. L. Pappagallo, I. Pilotti, S. Ausoni, M. Bari, F. Rosetti, D. Sartori, et al.
The Impact of Progenitor Enrichment, Serum, and Cytokines on the Ex Vivo Expansion of Mobilized Peripheral Blood Stem Cells: A Controlled Trial
Stem Cells,
January 1, 2003;
21(1):
33 - 40.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Richard and C. A. Blau
Small-Molecule-Directed Mpl Signaling Can Complement Growth Factors to Selectively Expand Genetically Modified Cord Blood Cells
Stem Cells,
January 1, 2003;
21(1):
71 - 78.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Piacibello, S. Bruno, F. Sanavio, S. Droetto, M. Gunetti, L. Ailles, F. S. de Sio, A. Viale, L. Gammaitoni, A. Lombardo, et al.
Lentiviral gene transfer and ex vivo expansion of human primitive stem cells capable of primary, secondary, and tertiary multilineage repopulation in NOD/SCID mice
Blood,
December 15, 2002;
100(13):
4391 - 4400.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Kuter and C. G. Begley
Recombinant human thrombopoietin: basic biology and evaluation of clinical studies
Blood,
November 15, 2002;
100(10):
3457 - 3469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Linden and K. Kaushansky
The Glycan Domain of Thrombopoietin (TPO) Acts in trans to Enhance Secretion of the Hormone and Other Cytokines
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
Stem Cells,
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
Addition of a second, different allogeneic graft accelerates white cell and platelet engraftment after T-cell-depleted bone marrow transplantation
Blood,
March 15, 2002;
99(6):
2235 - 2240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Dravid and S.G.A. Rao
Ex Vivo Expansion of Stem Cells from Umbilical Cord Blood: Expression of Cell Adhesion Molecules
Stem Cells,
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
J. Immunol.,
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]
|
|
|
|
