|
|
Previous Article | Table of Contents | Next Article 
Stromal fibroblast heparan sulfate is required for cytokine-mediated ex
vivo maintenance of human long-term culture-initiating cells
P Gupta, JB McCarthy and CM Verfaillie
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
We have recently demonstrated that 50% of primitive human long-term
culture-initiating cells (LTC-IC) are maintained for up to 8 weeks in
stroma-dependent cultures in which progenitor-stroma contact is prevented
(stroma noncontact), or when progenitors are cultured in medium conditioned
by stromal feeders. This indicates that factors responsible for LTC-IC
maintenance are present in soluble form in stromal supernatant (SN).
Although the picogram concentrations of cytokines present in stromal SN can
induce the differentiation of CD34+/HLA-DR- (DR-) cells to clonogenic cells
(colony forming cells; CFC), they maintain only 10% of LTC-IC for 5 weeks,
suggesting that factors other than these cytokines are required for LTC-IC
maintenance. To characterize the factor(s) in stromal SN responsible for
LTC-IC maintenance, we purified glycoproteins and proteoglycans (PG) from
the SN of the LTC-IC supportive murine marrow stromal fibroblast cell line
M2-10B4 by ion exchange high performance liquid chromatography (HPLC).
Culture of DR- cells in a combination of M2-10B4-derived PG, but not
glycoproteins and picogram concentrations of recombinant human
interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), stem
cell factor (SCF), leukemia inhibitory factor (LIF), granulocyte-
macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory
protein-1alpha (MIP-1alpha) resulted in the recovery of 96% +/- 8% of
LTC-IC maintained in cultures supplemented with unfractionated stromal SN.
LTC-IC maintenance was largely retained after digestion of the PG-rich
fraction with proteinase K and after dissociative gel filtration
chromatography, but was completely abolished following treatment with
nitrous acid, which digests heparan sulfate glycosaminoglycans (HS GAG). As
for M2-10B4-derived HS GAG, high concentrations of bovine kidney HS GAG,
but not bovine tracheal chondroitin sulfate, significantly improved
cytokine-mediated LTC-IC maintenance. Maintenance of LTC-IC by these
nonmarrow-derived HS GAG was, however, significantly lower than that seen
with M2-10B4-derived HS. These studies demonstrate a role for marrow
stroma-derived HS GAG in the long-term in vitro maintenance of human
LTC-IC. Further structure-function analysis of these HS GAG may have
important implications for ex vivo stem cell expansion and gene transfer
into hematopoietic progenitors.
Volume 87,
Issue 8,
pp. 3229-3236,
04/15/1996
Copyright © 1996 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:

|
 |

|
 |
 
H. Modi, T. McDonald, S. Chu, J.-K. Yee, S. J. Forman, and R. Bhatia
Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells
Blood,
June 15, 2007;
109(12):
5411 - 5421.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Pan, M. S. Nelson, M. Reyes, L. Koodie, J. J. Brazil, E. J. Stephenson, R. C. Zhao, C. Peters, S. B. Selleck, S. E. Stringer, et al.
Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells
Blood,
September 15, 2005;
106(6):
1956 - 1964.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. E. Stringer, M. S. Nelson, and P. Gupta
Identification of an MIP-1alpha -binding heparan sulfate oligosaccharide that supports long-term in vitro maintenance of human LTC-ICs
Blood,
March 15, 2003;
101(6):
2243 - 2245.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S.-I. Hung, A. C. Chang, I. Kato, and N.-C. A. Chang
Transient expression of Ym1, a heparin-binding lectin, during developmental hematopoiesis and inflammation
J. Leukoc. Biol.,
July 1, 2002;
72(1):
72 - 82.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Jacenko, D. W. Roberts, M. R. Campbell, P. M. McManus, C. J. Gress, and Z. Tao
Linking Hematopoiesis to Endochondral Skeletogenesis through Analysis of Mice Transgenic for Collagen X
Am. J. Pathol.,
June 1, 2002;
160(6):
2019 - 2034.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. S. Holtz, M. L. Slovak, F. Zhang, C. L. Sawyers, S. J. Forman, and R. Bhatia
Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation
Blood,
May 15, 2002;
99(10):
3792 - 3800.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Jacenko, D. Chan, A. Franklin, S. Ito, C. B. Underhill, J. F. Bateman, and M. R. Campbell
A Dominant Interference Collagen X Mutation Disrupts Hypertrophic Chondrocyte Pericellular Matrix and Glycosaminoglycan and Proteoglycan Distribution in Transgenic Mice
Am. J. Pathol.,
December 1, 2001;
159(6):
2257 - 2269.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bennaceur-Griscelli, C. Pondarre, V. Schiavon, W. Vainchenker, and L. Coulombel
Stromal cells retard the differentiation of CD34+CD38low/neg human primitive progenitors exposed to cytokines independent of their mitotic history
Blood,
January 15, 2001;
97(2):
435 - 441.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Jiang, R. C. H. Zhao, and C. M. Verfaillie
Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34+ cell proliferation: BCR/ABL up-regulates the cyclin-dependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity
PNAS,
September 5, 2000;
(2000)
190104497.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
C. J. Gress and O. Jacenko
Growth Plate Compressions and Altered Hematopoiesis in Collagen X Null Mice
J. Cell Biol.,
May 15, 2000;
149(4):
983 - 993.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Jiang, F. Prosper, and C. M. Verfaillie
Opposing effects of engagement of integrins and stimulation of cytokine receptors on cell cycle progression of normal human hematopoietic progenitors
Blood,
February 1, 2000;
95(3):
846 - 854.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Gupta, T. R. Oegema Jr, J. J. Brazil, A. Z. Dudek, A. Slungaard, and C. M. Verfaillie
Human LTC-IC can be maintained for at least 5 weeks in vitro when interleukin-3 and a single chemokine are combined with O-sulfated heparan sulfates: requirement for optimal binding interactions of heparan sulfate with early-acting cytokines and matrix proteins
Blood,
January 1, 2000;
95(1):
147 - 155.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Wettreich, A. Sebollela, M. A. Carvalho, S. P. Azevedo, R. Borojevic, S. T. Ferreira, and T. Coelho-Sampaio
Acidic pH Modulates the Interaction between Human Granulocyte-Macrophage Colony-stimulating Factor and Glycosaminoglycans
J. Biol. Chem.,
October 29, 1999;
274(44):
31468 - 31475.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bennaceur-Griscelli, C. Tourino, B. Izac, W. Vainchenker, and L. Coulombel
Murine Stromal Cells Counteract the Loss of Long-Term Culture-Initiating Cell Potential Induced by Cytokines in CD34+CD38low/neg Human Bone Marrow Cells
Blood,
July 15, 1999;
94(2):
529 - 538.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Yamashita, K. Oritani, E. K. Miyoshi, R. Wall, M. Bernfield, and P. W. Kincade
Syndecan-4 Is Expressed by B Lineage Lymphocytes and Can Transmit a Signal for Formation of Dendritic Processes
J. Immunol.,
May 15, 1999;
162(10):
5940 - 5948.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Drzeniek, G. Stocker, B. Siebertz, U. Just, T. Schroeder, W. Ostertag, and H.-D. Haubeck
Heparan Sulfate Proteoglycan Expression Is Induced During Early Erythroid Differentiation of Multipotent Hematopoietic Stem Cells
Blood,
May 1, 1999;
93(9):
2884 - 2897.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. Borghesi, Y. Yamashita, and P. W. Kincade
Heparan Sulfate Proteoglycans Mediate Interleukin-7- Dependent B Lymphopoiesis
Blood,
January 1, 1999;
93(1):
140 - 148.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Gupta, T. R. Oegema Jr, J. J. Brazil, A. Z. Dudek, A. Slungaard, and C. M. Verfaillie
Structurally Specific Heparan Sulfates Support Primitive Human Hematopoiesis by Formation of a Multimolecular Stem Cell Niche
Blood,
December 15, 1998;
92(12):
4641 - 4651.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. S. Miller, V. McCullar, and C. M. Verfaillie
Ex Vivo Culture of CD34+/Lin-/DR- Cells in Stroma-Derived Soluble Factors, Interleukin-3, and Macrophage Inflammatory Protein-1alpha Maintains Not Only Myeloid But Also Lymphoid Progenitors in a Novel Switch Culture Assay
Blood,
June 15, 1998;
91(12):
4516 - 4522.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Gupta, B. R. Blazar, K. Gupta, and C. M. Verfaillie
Human CD34+ Bone Marrow Cells Regulate Stromal Production of Interleukin-6 and Granulocyte Colony-Stimulating Factor and Increase the Colony-Stimulating Activity of Stroma
Blood,
May 15, 1998;
91(10):
3724 - 3733.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. P. Schofield, M. J. Humphries, E. de Wynter, N. Testa, and J. T. Gallagher
The Effect of alpha 4beta 1-Integrin Binding Sequences of Fibronectin on Growth of Cells From Human Hematopoietic Progenitors
Blood,
May 1, 1998;
91(9):
3230 - 3238.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Lai, F. Chen, S. McKenna, and I. Goldschneider
Identification of an IL-7-Associated Pre-Pro-B Cell Growth-Stimulating Factor (PPBSF). II. PPBSF Is a Covalently Linked Heterodimer of IL-7 and a Mr 30,000 Cofactor
J. Immunol.,
March 1, 1998;
160(5):
2280 - 2286.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Jiang, R. C. H. Zhao, and C. M. Verfaillie
Abnormal integrin-mediated regulation of chronic myelogenous leukemia CD34+ cell proliferation: BCR/ABL up-regulates the cyclin-dependent kinase inhibitor, p27Kip, which is relocated to the cell cytoplasm and incapable of regulating cdk2 activity
PNAS,
September 12, 2000;
97(19):
10538 - 10543.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|