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AC133, a Novel Marker for Human Hematopoietic Stem and Progenitor Cells

Amy H. Yin, Sheri Miraglia, Esmail D. Zanjani, Graca Almeida-Porada, Makio Ogawa, Anne G. Leary, Johanna Olweus, John Kearney, and David W. Buck

From AmCell Corp, Sunnyvale, CA; Veterans Administration Medical Center, University of Nevada, Reno, NV; Ralph H. Johnson Department of Veterans Affairs Medical Center and the Department of Medicine, Medical University of South Carolina, Charleston, SC; Becton Dickinson Immunocytometry Systems, San Jose, CA; and Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL.

AC133 is one of a new panel of murine hybridoma lines producing monoclonal IgG antibodies (mAbs) to a novel stem cell glycoprotein antigen with a molecular weight of 120 kD. AC133 antigen is selectively expressed on CD34bright hematopoietic stem and progenitor cells (progenitors) derived from human fetal liver and bone marrow, and blood. It is not detectable on other blood cells, cultured human umbilical vein endothelial cells (HUVECs), fibroblast cell lines, or the myeloid leukemia cell line KG1a by standard flow cytometric procedures. All of the noncommitted CD34+ cell population, as well as the majority of CD34+ cells committed to the granulocytic/monocytic pathway, are stained with AC133 antibody. In vitro clonogenicity assays have demonstrated that the CD34+AC133+ double-positive population from adult bone marrow contains the majority of the CFU-GM, a proportion of the CFU-Mix, and a minor population of BFU-E. The CD34dim and AC133- population has been shown to contain the remaining progenitor cells. AC133-selected cells engraft successfully in a fetal sheep transplantation model, and human cells harvested from chimeric fetal sheep bone marrow have been shown to successfully engraft secondary recipients, providing evidence for the long-term repopulating potential of AC133+ cells. A cDNA coding for AC133 antigen has been isolated, which codes for a polypeptide consisting of 865 amino acids (aa) with a predicted size of 97 kD. This antigen is modeled as a 5-transmembrane molecule, a structure that is novel among known cell surface structures. AC133 antibody provides an alternative to CD34 for the selection and characterization of cells necessary for both short- and long-term engraftment, in transplant situations, for studies of ex vivo expansion strategies, and for gene therapy.

Blood, Vol. 90 No. 12 (December 15), 1997: pp. 5002-5012
© 1997 by The American Society of Hematology.


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Cancer Res., May 15, 2005; 65(10): 4320 - 4333.
[Abstract] [Full Text] [PDF]


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CirculationHome page
S. V. Shmelkov, S. Meeus, N. Moussazadeh, P. Kermani, W. K. Rashbaum, S. Y. Rabbany, M. A. Hanson, W. J. Lane, R. St. Clair, K. A. Walsh, et al.
Cytokine Preconditioning Promotes Codifferentiation of Human Fetal Liver CD133+ Stem Cells Into Angiomyogenic Tissue
Circulation, March 8, 2005; 111(9): 1175 - 1183.
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J. Immunol.Home page
T. Hieronymus, T. C. Gust, R. D. Kirsch, T. Jorgas, G. Blendinger, M. Goncharenko, K. Supplitt, S. Rose-John, A. M. Muller, and M. Zenke
Progressive and Controlled Development of Mouse Dendritic Cells from Flt3+CD11b+ Progenitors In Vitro
J. Immunol., March 1, 2005; 174(5): 2552 - 2562.
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Cancer Res.Home page
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.
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Am. J. Pathol.Home page
B. Bussolati, S. Bruno, C. Grange, S. Buttiglieri, M. C. Deregibus, D. Cantino, and G. Camussi
Isolation of Renal Progenitor Cells from Adult Human Kidney
Am. J. Pathol., February 1, 2005; 166(2): 545 - 555.
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Arterioscler. Thromb. Vasc. Bio.Home page
T. M. Powell, J. D. Paul, J. M. Hill, M. Thompson, M. Benjamin, M. Rodrigo, J. P. McCoy, E. J. Read, H. M. Khuu, S. F. Leitman, et al.
Granulocyte Colony-Stimulating Factor Mobilizes Functional Endothelial Progenitor Cells in Patients With Coronary Artery Disease
Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 296 - 301.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
S. Davani, F. Deschaseaux, D. Chalmers, P. Tiberghien, and J.-P. Kantelip
Can stem cells mend a broken heart?
Cardiovasc Res, February 1, 2005; 65(2): 305 - 316.
[Abstract] [Full Text] [PDF]


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BloodHome page
M. A. Vodyanik, J. A. Bork, J. A. Thomson, and I. I. Slukvin
Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential
Blood, January 15, 2005; 105(2): 617 - 626.
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BloodHome page
M. Massa, V. Rosti, M. Ferrario, R. Campanelli, I. Ramajoli, R. Rosso, G. M. De Ferrari, M. Ferlini, L. Goffredo, A. Bertoletti, et al.
Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction
Blood, January 1, 2005; 105(1): 199 - 206.
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Br. J. Radiol.Home page
I B Resnick and S Slavin
Lessons from bone marrow transplantation for a victim of a radiological accident with acute radiation syndrome
Br. J. Radiol., January 1, 2005; Supplement_27(1): 21 - 25.
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CirculationHome page
G. Nowak, A. Karrar, C. Holmen, S. Nava, M. Uzunel, K. Hultenby, and S. Sumitran-Holgersson
Expression of Vascular Endothelial Growth Factor Receptor-2 or Tie-2 on Peripheral Blood Cells Defines Functionally Competent Cell Populations Capable of Reendothelialization
Circulation, December 14, 2004; 110(24): 3699 - 3707.
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B. Giebel, D. Corbeil, J. Beckmann, J. Hohn, D. Freund, K. Giesen, J. Fischer, G. Kogler, and P. Wernet
Segregation of lipid raft markers including CD133 in polarized human hematopoietic stem and progenitor cells
Blood, October 15, 2004; 104(8): 2332 - 2338.
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BloodHome page
G. Almeida-Porada, C. D. Porada, J. Chamberlain, A. Torabi, and E. D. Zanjani
Formation of human hepatocytes by human hematopoietic stem cells in sheep
Blood, October 15, 2004; 104(8): 2582 - 2590.
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BloodHome page
D. A. Hess, T. E. Meyerrose, L. Wirthlin, T. P. Craft, P. E. Herrbrich, M. H. Creer, and J. A. Nolta
Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity
Blood, September 15, 2004; 104(6): 1648 - 1655.
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J. Clin. Pathol.Home page
W Hilbe, S Dirnhofer, F Oberwasserlechner, T Schmid, E Gunsilius, G Hilbe, E Woll, and C M Kahler
CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer
J. Clin. Pathol., September 1, 2004; 57(9): 965 - 969.
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J. Cell Sci.Home page
C. A. Fargeas, A. Joester, E. Missol-Kolka, A. Hellwig, W. B. Huttner, and D. Corbeil
Identification of novel Prominin-1/CD133 splice variants with alternative C-termini and their expression in epididymis and testis
J. Cell Sci., August 15, 2004; 117(18): 4301 - 4311.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
X. Wu, E. Rabkin-Aikawa, K. J. Guleserian, T. E. Perry, Y. Masuda, F. W. H. Sutherland, F. J. Schoen, J. E. Mayer Jr., and J. Bischoff
Tissue-engineered microvessels on three-dimensional biodegradable scaffolds using human endothelial progenitor cells
Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H480 - H487.
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W. Wagner, A. Ansorge, U. Wirkner, V. Eckstein, C. Schwager, J. Blake, K. Miesala, J. Selig, R. Saffrich, W. Ansorge, et al.
Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis
Blood, August 1, 2004; 104(3): 675 - 686.
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CirculationHome page
A. Miranville, C. Heeschen, C. Sengenes, C.A. Curat, R. Busse, and A. Bouloumie
Improvement of Postnatal Neovascularization by Human Adipose Tissue-Derived Stem Cells
Circulation, July 20, 2004; 110(3): 349 - 355.
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J. Cell Sci.Home page
G. D. Richardson, C. N. Robson, S. H. Lang, D. E. Neal, N. J. Maitland, and A. T. Collins
CD133, a novel marker for human prostatic epithelial stem cells
J. Cell Sci., July 15, 2004; 117(16): 3539 - 3545.
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S. V. Shmelkov, L. Jun, R. St Clair, D. McGarrigle, C. A. Derderian, J. K. Usenko, C. Costa, F. Zhang, X. Guo, and S. Rafii
Alternative promoters regulate transcription of the gene that encodes stem cell surface protein AC133
Blood, March 15, 2004; 103(6): 2055 - 2061.
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J. Biol. Chem.Home page
N. Y. Frank, S. S. Pendse, P. H. Lapchak, A. Margaryan, D. Shlain, C. Doeing, M. H. Sayegh, and M. H. Frank
Regulation of Progenitor Cell Fusion by ABCB5 P-glycoprotein, a Novel Human ATP-binding Cassette Transporter
J. Biol. Chem., November 21, 2003; 278(47): 47156 - 47165.
[Abstract] [Full Text] [PDF]


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J. Appl. Physiol.Home page
K. Yamamoto, T. Takahashi, T. Asahara, N. Ohura, T. Sokabe, A. Kamiya, and J. Ando
Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress
J Appl Physiol, November 1, 2003; 95(5): 2081 - 2088.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
S. K. Singh, I. D. Clarke, M. Terasaki, V. E. Bonn, C. Hawkins, J. Squire, and P. B. Dirks
Identification of a Cancer Stem Cell in Human Brain Tumors
Cancer Res., September 15, 2003; 63(18): 5821 - 5828.
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BloodHome page
G. N. Schwartz, B. A. Vance, B. M. Levine, M. Fukazawa, W. G. Telford, D. Cesar, M. Hellerstein, and R. E. Gress
Proliferation kinetics of subpopulations of human marrow cells determined by quantifying in vivo incorporation of [2H2]-glucose into DNA of S-phase cells
Blood, September 15, 2003; 102(6): 2068 - 2073.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
M. Hristov, W. Erl, and P. C. Weber
Endothelial Progenitor Cells: Mobilization, Differentiation, and Homing
Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1185 - 1189.
[Abstract] [Full Text] [PDF]


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CirculationHome page
P. E. Szmitko, P. W.M. Fedak, R. D. Weisel, D. J. Stewart, M. J.B. Kutryk, and S. Verma
Endothelial Progenitor Cells: New Hope for a Broken Heart
Circulation, June 24, 2003; 107(24): 3093 - 3100.
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J. Neurosci.Home page
J. M. Angelastro, T. N. Ignatova, V. G. Kukekov, D. A. Steindler, G. B. Stengren, C. Mendelsohn, and L. A. Greene
Regulated Expression of ATF5 Is Required for the Progression of Neural Progenitor Cells to Neurons
J. Neurosci., June 1, 2003; 23(11): 4590 - 4600.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
H. Masuda and T. Asahara
Post-natal endothelial progenitor cells for neovascularization in tissue regeneration
Cardiovasc Res, May 1, 2003; 58(2): 390 - 398.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
J. Eggermann, S. Kliche, G. Jarmy, K. Hoffmann, U. Mayr-Beyrle, K.-M. Debatin, J. Waltenberger, and C. Beltinger
Endothelial progenitor cell culture and differentiation in vitro: a methodological comparison using human umbilical cord blood
Cardiovasc Res, May 1, 2003; 58(2): 478 - 486.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
D. Nakul-Aquaronne, J. Bayle, and C. Frelin
Coexpression of endothelial markers and CD14 by cytokine mobilized CD34+ cells under angiogenic stimulation
Cardiovasc Res, March 1, 2003; 57(3): 816 - 823.
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J. Biol. Chem.Home page
C. A. Fargeas, M. Florek, W. B. Huttner, and D. Corbeil
Characterization of Prominin-2, a New Member of the Prominin Family of Pentaspan Membrane Glycoproteins
J. Biol. Chem., February 28, 2003; 278(10): 8586 - 8596.
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BloodHome page
S. Kuci, J. T. Wessels, H.-J. Buhring, K. Schilbach, M. Schumm, G. Seitz, J. Loffler, P. Bader, P. G. Schlegel, D. Niethammer, et al.
Identification of a novel class of human adherent CD34- stem cells that give rise to SCID-repopulating cells
Blood, February 1, 2003; 101(3): 869 - 876.
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ASH Education BookHome page
M. H. Cottler-Fox, T. Lapidot, I. Petit, O. Kollet, J. F. DiPersio, D. Link, and S. Devine
Stem Cell Mobilization
Hematology, January 1, 2003; 2003(1): 419 - 437.
[Abstract] [Full Text] [PDF]


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BloodHome page
P. Salven, S. Mustjoki, R. Alitalo, K. Alitalo, and S. Rafii
VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells
Blood, January 1, 2003; 101(1): 168 - 172.
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P. E. Burger, S. Coetzee, W. L. McKeehan, M. Kan, P. Cook, Y. Fan, T. Suda, R. P. Hebbel, N. Novitzky, W. A. Muller, et al.
Fibroblast growth factor receptor-1 is expressed by endothelial progenitor cells
Blood, November 15, 2002; 100(10): 3527 - 3535.
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