|
|
 Previous Article | Table of Contents | Next Article 
In vitro maintenance of highly purified, transplantable hematopoietic stem
cells
KA Moore, H Ema and IR Lemischka
Department of Molecular Biology, Princeton University, NJ 08544, USA.
The cellular and molecular mechanisms that regulate the most primitive
hematopoietic stem cell are not well understood. We have undertaken a
systematic dissection of the complex hematopoietic microenvironment to
define some of these mechanisms. An extensive panel of immortalized stromal
cell lines from murine fetal liver were established and characterized.
Collectively, these cell lines display extensive heterogeneity in their in
vitro hematopoietic supportive capacity. In the current studies, we
describe a long-term in vitro culture system using a single stromal cell
clone (AFT024) that qualitatively and quantitatively supports
transplantable stem cell activity present in highly purified populations.
We show multilineage reconstitution in mice that received the equivalent of
as few as 100 purified bone marrow and fetal liver stem cells cultured for
4 to 7 weeks on AFT024. The cultured stem cells meet all functional
criteria currently ascribed to the most primitive stem cell population. The
levels of stem cell activity present after 5 weeks of coculture with AFT024
far exceed those present in short-term cytokine-supported cultures. In
addition, maintenance of input levels of transplantable stem cell activity
is accompanied by expansion of other classes of stem/progenitor cells. This
suggests that the stem/progenitor cell population is actively proliferating
in culture and that the AFT024 cell line provides a milieu that stimulates
progenitor cell proliferation while maintaining in vivo repopulating
activity.
Volume 89,
Issue 12,
pp. 4337-4347,
06/15/1997
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:
|
|
|
|
 
D. Bhattacharya, A. Czechowicz, A.G. L. Ooi, D. J. Rossi, D. Bryder, and I. L. Weissman
Niche recycling through division-independent egress of hematopoietic stem cells
J. Exp. Med.,
November 11, 2009;
(2009)
jem.20090778v3.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. W. Lane, D. T. Scadden, and D. G. Gilliland
The leukemic stem cell niche: current concepts and therapeutic opportunities
Blood,
August 6, 2009;
114(6):
1150 - 1157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Kent, M. R. Copley, C. Benz, S. Wohrer, B. J. Dykstra, E. Ma, J. Cheyne, Y. Zhao, M. B. Bowie, Y. Zhao, et al.
Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential
Blood,
June 18, 2009;
113(25):
6342 - 6350.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Orelio, M. Peeters, E. Haak, K. van der Horn, and E. Dzierzak
Interleukin-1 regulates hematopoietic progenitor and stem cells in the midgestation mouse fetal liver
Haematologica,
April 1, 2009;
94(4):
462 - 469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Perry, O. F. Harandi, P. Porayette, S. Hegde, A. K. Kannan, and R. F. Paulson
Maintenance of the BMP4-dependent stress erythropoiesis pathway in the murine spleen requires hedgehog signaling
Blood,
January 22, 2009;
113(4):
911 - 918.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ema and H. Nakauchi
Bloodlines of haematopoietic stem cell research in Japan
Phil Trans R Soc B,
June 27, 2008;
363(1500):
2089 - 2097.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Durand, C. Robin, K. Bollerot, M. H. Baron, K. Ottersbach, and E. Dzierzak
Embryonic stromal clones reveal developmental regulators of definitive hematopoietic stem cells
PNAS,
December 26, 2007;
104(52):
20838 - 20843.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Beckmann, S. Scheitza, P. Wernet, J. C. Fischer, and B. Giebel
Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins
Blood,
June 15, 2007;
109(12):
5494 - 5501.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Bowie, D. G. Kent, M. R. Copley, and C. J. Eaves
Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells
Blood,
June 1, 2007;
109(11):
5043 - 5048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Nygren, D. Bryder, and S. E. W. Jacobsen
Prolonged Cell Cycle Transit Is a Defining and Developmentally Conserved Hemopoietic Stem Cell Property
J. Immunol.,
July 1, 2006;
177(1):
201 - 208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Giebel, T. Zhang, J. Beckmann, J. Spanholtz, P. Wernet, A. D. Ho, and M. Punzel
Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division
Blood,
March 1, 2006;
107(5):
2146 - 2152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Woll, C. H. Martin, J. S. Miller, and D. S. Kaufman
Human Embryonic Stem Cell-Derived NK Cells Acquire Functional Receptors and Cytolytic Activity
J. Immunol.,
October 15, 2005;
175(8):
5095 - 5103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Storms, P. D. Green, K. M. Safford, D. Niedzwiecki, C. R. Cogle, O. M. Colvin, N. J. Chao, H. E. Rice, and C. A. Smith
Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34
Blood,
July 1, 2005;
106(1):
95 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Zhang and H. F. Lodish
Murine hematopoietic stem cells change their surface phenotype during ex vivo expansion
Blood,
June 1, 2005;
105(11):
4314 - 4320.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Taichman
Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche
Blood,
April 1, 2005;
105(7):
2631 - 2639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. C. Mendes, C. Robin, and E. Dzierzak
Mesenchymal progenitor cells localize within hematopoietic sites throughout ontogeny
Development,
March 1, 2005;
132(5):
1127 - 1136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. S. Oh, A. Moharita, J. G. Potian, I. P. Whitehead, J. C. Livingston, T. A. Castro, P. S. Patel, and P. Rameshwar
Bone Marrow Stroma Influences Transforming Growth Factor-{beta} Production in Breast Cancer Cells to Regulate c-myc Activation of the Preprotachykinin-I Gene in Breast Cancer Cells
Cancer Res.,
September 1, 2004;
64(17):
6327 - 6336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kubota, M. R. Avarbock, and R. L. Brinster
Culture Conditions and Single Growth Factors Affect Fate Determination of Mouse Spermatogonial Stem Cells
Biol Reprod,
September 1, 2004;
71(3):
722 - 731.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Goodrum, C. T. Jordan, S. S. Terhune, K. High, and T. Shenk
Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations
Blood,
August 1, 2004;
104(3):
687 - 695.
[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]
|
|
|
|
|
|
|
G. Rao, P. S. Patel, S. P. Idler, P. Maloof, P. Gascon, J. A. Potian, and P. Rameshwar
Facilitating Role of Preprotachykinin-I Gene in the Integration of Breast Cancer Cells within the Stromal Compartment of the Bone Marrow: A Model of Early Cancer Progression
Cancer Res.,
April 15, 2004;
64(8):
2874 - 2881.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Zhang and H. F. Lodish
Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells
Blood,
April 1, 2004;
103(7):
2513 - 2521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Melani, C. Chiodoni, G. Forni, and M. P. Colombo
Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity
Blood,
September 15, 2003;
102(6):
2138 - 2145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chagraoui, A. Lepage-Noll, A. Anjo, G. Uzan, and P. Charbord
Fetal liver stroma consists of cells in epithelial-to-mesenchymal transition
Blood,
April 15, 2003;
101(8):
2973 - 2982.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kawano, M. Kobune, M. Yamaguchi, K. Nakamura, Y. Ito, K. Sasaki, S. Takahashi, T. Nakamura, H. Chiba, T. Sato, et al.
Ex vivo expansion of human umbilical cord hematopoietic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)-transfected human stromal cells
Blood,
January 15, 2003;
101(2):
532 - 540.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. D. Goodrum, C. T. Jordan, K. High, and T. Shenk
Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: A model for latency
PNAS,
December 10, 2002;
99(25):
16255 - 16260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Carlo-Stella, M. Di Nicola, M. Magni, P. Longoni, M. Milanesi, C. Stucchi, L. Cleris, F. Formelli, and M. A. Gianni
Defibrotide in Combination with Granulocyte Colony-stimulating Factor Significantly Enhances the Mobilization of Primitive and Committed Peripheral Blood Progenitor Cells in Mice
Cancer Res.,
November 1, 2002;
62(21):
6152 - 6157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Hackney, P. Charbord, B. P. Brunk, C. J. Stoeckert, I. R. Lemischka, and K. A. Moore
A molecular profile of a hematopoietic stem cell niche
PNAS,
October 1, 2002;
99(20):
13061 - 13066.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Oberlin, M. Tavian, I. Blazsek, and B. Peault
Blood-forming potential of vascular endothelium in the human embryo
Development,
September 1, 2002;
129(17):
4147 - 4157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. J. Oostendorp, A. J. Medvinsky, N. Kusadasi, N. Nakayama, K. Harvey, C. Orelio, K. Ottersbach, T. Covey, R. E. Ploemacher, C. Saris, et al.
Embryonal subregion-derived stromal cell lines from novel temperature-sensitive SV40 T antigen transgenic mice support hematopoiesis
J. Cell Sci.,
May 15, 2002;
115(10):
2099 - 2108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Pinto do O, K. Richter, and L. Carlsson
Hematopoietic progenitor/stem cells immortalized by Lhx2 generate functional hematopoietic cells in vivo
Blood,
May 13, 2002;
99(11):
3939 - 3946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. J. Oostendorp, K. N. Harvey, N. Kusadasi, M. F. T. R. de Bruijn, C. Saris, R. E. Ploemacher, A. L. Medvinsky, and E. A. Dzierzak
Stromal cell lines from mouse aorta-gonads-mesonephros subregions are potent supporters of hematopoietic stem cell activity
Blood,
February 15, 2002;
99(4):
1183 - 1189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Nakajima, R. Zhao, T. C. Lund, J. Ward, M. Dolan, B. Hirsch, and J. S. Miller
The BCR/ABL Transgene Causes Abnormal NK Cell Differentiation and Can Be Found in Circulating NK Cells of Advanced Phase Chronic Myelogenous Leukemia Patients
J. Immunol.,
January 15, 2002;
168(2):
643 - 650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Kumaravelu, L. Hook, A. M. Morrison, J. Ure, S. Zhao, S. Zuyev, J. Ansell, and A. Medvinsky
Quantitative developmental anatomy of definitive haematopoietic stem cells/long-term repopulating units (HSC/RUs): role of the aorta-gonad-mesonephros (AGM) region and the yolk sac in colonisation of the mouse embryonic liver
Development,
January 11, 2002;
129(21):
4891 - 4899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Reyes, T. Lund, T. Lenvik, D. Aguiar, L. Koodie, and C. M. Verfaillie
Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells
Blood,
November 1, 2001;
98(9):
2615 - 2625.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller and V. McCullar
Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2
Blood,
August 1, 2001;
98(3):
705 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. T. Chu and F. H. Gage
Chipping away at stem cells
PNAS,
July 3, 2001;
98(14):
7652 - 7653.
[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]
|
|
|
|
|
|
|
H.-C. Hsu, H. Ema, M. Osawa, Y. Nakamura, T. Suda, and H. Nakauchi
Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver
Blood,
December 1, 2000;
96(12):
3757 - 3762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Yanai, N. Matsui, T. Furusawa, T. Okubo, and M. Obinata
Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive hematopoietic cells into stromal cell layers
Blood,
July 1, 2000;
96(1):
139 - 144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kirby, W. Walton, and O. Smithies
Hematopoietic stem cells with controllable tEpoR transgenes have a competitive advantage in bone marrow transplantation
Blood,
June 15, 2000;
95(12):
3710 - 3715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Phillips, R. E. Ernst, B. Brunk, N. Ivanova, M. A. Mahan, J. K. Deanehan, K. A. Moore, G. C. Overton, and I. R. Lemischka
The Genetic Program of Hematopoietic Stem Cells
Science,
June 2, 2000;
288(5471):
1635 - 1640.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
C.-C. Shih, M. C.-T. Hu, J. Hu, J. Medeiros, and S. J. Forman
Long-Term Ex Vivo Maintenance and Expansion of Transplantable Human Hematopoietic Stem Cells
Blood,
September 1, 1999;
94(5):
1623 - 1636.
[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]
|
|
|
|
|
|
|
M. Yagi, K. A. Ritchie, E. Sitnicka, C. Storey, G. J. Roth, and S. Bartelmez
Sustained ex vivo expansion of hematopoietic stem cells mediated by thrombopoietin
PNAS,
July 6, 1999;
96(14):
8126 - 8131.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Punzel, S.D. Wissink, J.S. Miller, K.A. Moore, I.R. Lemischka, and C.M. Verfaillie
The Myeloid-Lymphoid Initiating Cell (ML-IC) Assay Assesses the Fate of Multipotent Human Progenitors In Vitro
Blood,
June 1, 1999;
93(11):
3750 - 3756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Szilvassy, M. J. Bass, G. Van Zant, and B. Grimes
Organ-Selective Homing Defines Engraftment Kinetics of Murine Hematopoietic Stem Cells and Is Compromised by Ex Vivo Expansion
Blood,
March 1, 1999;
93(5):
1557 - 1566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller, V. McCullar, M. Punzel, I. R. Lemischka, and K. A. Moore
Single Adult Human CD34+/Lin-/CD38- Progenitors Give Rise to Natural Killer Cells, B-Lineage Cells, Dendritic Cells, and Myeloid Cells
Blood,
January 1, 1999;
93(1):
96 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-j. Xu, K. Tsuji, T. Ueda, Y.-s. Mukouyama, T. Hara, F.-C. Yang, Y. Ebihara, S. Matsuoka, A. Manabe, A. Kikuchi, et al.
Stimulation of Mouse and Human Primitive Hematopoiesis by Murine Embryonic Aorta-Gonad-Mesonephros-Derived Stromal Cell Lines
Blood,
September 15, 1998;
92(6):
2032 - 2040.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.F. Tisdale, Y. Hanazono, S.E. Sellers, B.A. Agricola, M.E. Metzger, R.E. Donahue, and C.E. Dunbar
Ex Vivo Expansion of Genetically Marked Rhesus Peripheral Blood Progenitor Cells Results in Diminished Long-Term Repopulating Ability
Blood,
August 15, 1998;
92(4):
1131 - 1141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Ohneda, C. Fennie, Z. Zheng, C. Donahue, H. La, R. Villacorta, B. Cairns, and L. A. Lasky
Hematopoietic Stem Cell Maintenance and Differentiation Are Supported by Embryonic Aorta-Gonad-Mesonephros Region-Derived Endothelium
Blood,
August 1, 1998;
92(3):
908 - 919.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Varnum-Finney, L. E. Purton, M. Yu, C. Brashem-Stein, D. Flowers, S. Staats, K. A. Moore, I. Le Roux, R. Mann, G. Gray, et al.
The Notch Ligand, Jagged-1, Influences the Development of Primitive Hematopoietic Precursor Cells
Blood,
June 1, 1998;
91(11):
4084 - 4091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Wlodarski, M. Wasik, M. Z. Ratajczak, C. Sevignani, G. Hoser, J. Kawiak, A. M. Gewirtz, B. Calabretta, and T. Skorski
Role of p53 in Hematopoietic Recovery After Cytotoxic Treatment
Blood,
April 15, 1998;
91(8):
2998 - 3006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
