| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 158, Issue 11 5169-5177, Copyright © 1997 by American Association of Immunologists
ARTICLES |
V Ramsfjell, OJ Borge, L Cui and SE Jacobsen
Hipple Cancer Research Center, Dayton, OH 45439, USA. Veslemoy.Ramsfjell@med.lu.se
Thrombopoietin (Tpo) is a primary regulator of megakaryocyte and platelet production. However, studies in c-mpl-deficient mice suggest that Tpo might also play an important role in early hemopoiesis. Here, the direct ability of Tpo to stimulate stroma-independent growth, multilineage differentiation, and progenitor cell expansion from single primitive CD34+ CD38- human bone marrow cells was investigated. Tpo alone stimulated limited clonal growth, but synergized with c-kit ligand (KL), flt3 ligand (FL), or IL-3 to potently enhance clonogenic growth. Whereas KL and FL in combination stimulated the clonal growth of only 3% of CD34+ CD38- cells, 40% of CD34+ CD38- cells were recruited by KL+FL+Tpo, demonstrating that Tpo promotes the growth of a high fraction of CD34+ CD38- progenitor cells. Additional cytokines (IL- 3, IL-6, and erythropoietin (Epo)) did not significantly enhance clonal growth above that observed in response to KL+FL+Tpo. In contrast, Tpo enhanced clonogenic growth in response to KL+FL+IL-3+IL-6+Epo by as much as 80%, implicating a key role for this cytokine in early hemopoiesis. Importantly, we also demonstrate that the majority of Tpo- recruited CD34+ CD38- progenitor cells have a multilineage differentiation potential, and that Tpo promotes prolonged expansion of multipotent progenitors. Specifically, whereas progenitor cells were reduced in cultures containing only KL+FL, addition of Tpo resulted in 40-fold expansion of multipotent progenitors following a 14-day incubation. Finally, we identified inhibitors of Tpo-induced progenitor cell growth, in that TGF-beta as well as TNF-alpha almost completely abrogated the growth of CD34+ CD38- progenitor cells in response to Tpo alone as well as KL+FL+Tpo.
This article has been cited by other articles:
|
|
 |
|
  M. Jaras, A. Edqvist, J. Rebetz, L. G. Salford, B. Widegren, and X. Fan Human short-term repopulating cells have enhanced telomerase reverse transcriptase expression Blood, August 1, 2006; 108(3): 1084 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Saito, M. Hirokawa, K. Inaba, H. Fukaya, Y. Kawabata, A. Komatsuda, J. Yamashita, and K. Sawada Phagocytosis of codeveloping megakaryocytic progenitors by dendritic cells in culture with thrombopoietin and tumor necrosis factor-{alpha} and its possible role in hemophagocytic syndrome Blood, February 15, 2006; 107(4): 1366 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Langer, E. Henckaerts, J. Orenstein, and H.-W. Snoeck Quantitative Trait Analysis Reveals Transforming Growth Factor-{beta}2 as a Positive Regulator of Early Hematopoietic Progenitor and Stem Cell Function J. Exp. Med., January 5, 2004; 199(1): 5 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Akel, C. Petrow-Sadowski, M. J. Laughlin, and F. W. Ruscetti Neutralization of Autocrine Transforming Growth Factor-{beta} in Human Cord Blood CD34+CD38-Lin- Cells Promotes Stem-Cell-Factor-Mediated Erythropoietin-Independent Early Erythroid Progenitor Development and Reduces Terminal Differentiation Stem Cells, September 1, 2003; 21(5): 557 - 567. [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]
|
|
|
|
|
|
R. C.R. Perlingeiro, M. Kyba, S. Bodie, and G. Q. Daley A Role for Thrombopoietin in Hemangioblast Development Stem Cells, May 1, 2003; 21(3): 272 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Nilsson, I. Astrand-Grundstrom, K. Anderson, I. Arvidsson, P. Hokland, D. Bryder, L. Kjeldsen, B. Johansson, E. Hellstrom-Lindberg, R. Hast, et al. Involvement and functional impairment of the CD34+CD38-Thy-1+ hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8 Blood, June 17, 2002; 100(1): 259 - 267. [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]
|
|
|
|
 |
|
 G. A. Millot, W. Vainchenker, D. Dumenil, and F. Svinarchuk Distinct effects of thrombopoietin depending on a threshold level of activated Mpl in BaF-3 cells J. Cell Sci., January 6, 2002; 115(11): 2329 - 2337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
I. Dybedal, D. Bryder, A. Fossum, L. S. Rusten, and S. E. W. Jacobsen Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells Blood, September 15, 2001; 98(6): 1782 - 1791. [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]
|
|
|
|
|
|
I.-H. Oh, A. Lau, and C. J. Eaves During ontogeny primitive (CD34+CD38-) hematopoietic cells show altered expression of a subset of genes associated with early cytokine and differentiation responses of their adult counterparts Blood, December 15, 2000; 96(13): 4160 - 4168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Nilsson, I. Astrand-Grundstrom, I. Arvidsson, B. Jacobsson, E. Hellstrom-Lindberg, R. Hast, and S. E. W. Jacobsen Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level Blood, September 15, 2000; 96(6): 2012 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. O. Fortunel, A. Hatzfeld, and J. A. Hatzfeld Transforming growth factor-beta : pleiotropic role in the regulation of hematopoiesis Blood, September 15, 2000; 96(6): 2022 - 2036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. J. Oostendorp, J. Audet, and C. J. Eaves High-resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo Blood, February 1, 2000; 95(3): 855 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ramsfjell, D. Bryder, H. Bjorgvinsdottir, S. Kornfalt, L. Nilsson, O. J. Borge, and S. E.W. Jacobsen Distinct Requirements for Optimal Growth and In Vitro Expansion of Human CD34+CD38- Bone Marrow Long-Term Culture-Initiating Cells (LTC-IC), Extended LTC-IC, and Murine In Vivo Long-Term Reconstituting Stem Cells Blood, December 15, 1999; 94(12): 4093 - 4102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Verhasselt, T. Kerre, E. Naessens, D. Vanhecke, M. De Smedt, B. Vandekerckhove, and J. Plum Thymic Repopulation by CD34+ Human Cord Blood Cells After Expansion in Stroma-Free Culture Blood, December 1, 1999; 94(11): 3644 - 3652. [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]
|
|
|
|
|
|
J.-F. Arrighi, C. Hauser, B. Chapuis, R. H. Zubler, and V. Kindler Long-Term Culture of Human CD34+ Progenitors With FLT3-Ligand, Thrombopoietin, and Stem Cell Factor Induces Extensive Amplification of a CD34-CD14- and a CD34-CD14+ Dendritic Cell Precursor Blood, April 1, 1999; 93(7): 2244 - 2252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Goff, D. S. Shields, and J. S. Greenberger Influence of Cytokines on the Growth Kinetics and Immunophenotype of Daughter Cells Resulting From the First Division of Single CD34+Thy-1+lin- Cells Blood, December 1, 1998; 92(11): 4098 - 4107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wagemaker, K. J. Neelis, S. C.C. Hartong, A. W. Wognum, G. R. Thomas, P. J. Fielder, and D. L. Eaton The Efficacy of Recombinant Thrombopoietin in Murine and Nonhuman Primate Models for Radiation-Induced Myelosuppression and Stem Cell Transplantation Stem Cells, November 1, 1998; 16(6): 375 - 386. [Abstract] [Full Text]
|
|
|
|
|
|
K. J. Neelis, T. P. Visser, W. Dimjati, G. R. Thomas, P. J. Fielder, D. Bloedow, D. L. Eaton, and G. Wagemaker A Single Dose of Thrombopoietin Shortly After Myelosuppressive Total Body Irradiation Prevents Pancytopenia in Mice by Promoting Short-Term Multilineage Spleen-Repopulating Cells at the Transient Expense of Bone Marrow-Repopulating Cells Blood, September 1, 1998; 92(5): 1586 - 1597. [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]
|
|
|
|
|
|
G. P. Solar, W. G. Kerr, F. C. Zeigler, D. Hess, C. Donahue, F. J. de Sauvage, and D. L. Eaton Role of c-mpl in Early Hematopoiesis Blood, July 1, 1998; 92(1): 4 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Tacchini-Cottier, C. Vesin, M. Redard, W. Buurman, and P. F. Piguet Role of TNFR1 and TNFR2 in TNF-Induced Platelet Consumption in Mice J. Immunol., June 15, 1998; 160(12): 6182 - 6186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Lyman and S. E. W. Jacobsen c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities Blood, February 15, 1998; 91(4): 1101 - 1134. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Dao, A. J. Shah, G. M. Crooks, and J. A. Nolta Engraftment and Retroviral Marking of CD34+ and CD34+CD38- Human Hematopoietic Progenitors Assessed in Immune-Deficient Mice Blood, February 15, 1998; 91(4): 1243 - 1255. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
