Abstract
Lifelong hematopoiesis is sustained by a very small number of hematopoietic stem cells capable of self-renewal and differentiation into multiple hematopoietic lineages. The sialomucin CD34 has been, and is currently, used for the identification and purification of primitive hematopoietic progenitors. Depending on the source of stem cells, CD34 may not be expressed on all progenitor cells. An alternative stem cell marker is prominin-1 (CD133), which is expressed on a subpopulation of CD34+ cells as well as on CD34– progenitor cells derived from various sources including fetal liver and bone marrow, adult bone marrow, cord blood, and mobilized peripheral blood. CD133+ stem cells can reconstitute myelo- and lymphopoiesis of lethally irradiated mice, and the characterization of the CD133 expression on stem cells provides some insights into the biology of the hierarchy and functional organization of human hematopoiesis. The availability of methods for clinical large-scale isolation of CD133+ cells facilitates their use in autologous and allogeneic hematopoietic stem cell transplantation and possibly in other fields of regenerative medicine.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH (1984) Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol 133:157–165
Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE (1997) Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A 94:5320–5325
Krause DS, Fackler MJ, Civin CI, May WS (1996) CD34: structure, biology, and clinical utility. Blood 87:1–13
Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G, Grupp SA, Sieff CA, Mulligan RC, Johnson RP (1997) Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med 3:1337–1345
Zanjani ED, meida-Porada G, Livingston AG, Flake AW, Ogawa M (1998) Human bone marrow CD34- cells engraft in vivo and undergo multilineage expression that includes giving rise to CD34+ cells. Exp Hematol 26:353–360
Bhatia M, Bonnet D, Murdoch B, Gan OI, Dick JE (1998) A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med 4:1038–1045
Yin AH, Miraglia S, Zanjani ED, meida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012
Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, Bray RA, Waller EK, Buck DW (1997) A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90:5013–5021
Meregalli M, Farini A, Belicchi M, Torrente Y (2010) CD133(+) cells isolated from various sources and their role in future clinical perspectives. Expert Opin Biol Ther 10:1521–1528
Bauer N, Fonseca AV, Florek M, Freund D, Jászai J, Bornhäuser M, Fargeas CA, Corbeil D (2008) New insights into the cell biology of hematopoietic progenitors by studying prominin-1 (CD133). Cells Tissues Organs 188:127–138
de Wynter EA, Buck D, Hart C, Heywood R, Coutinho LH, Clayton A, Rafferty JA, Burt D, Guenechea G, Bueren JA, Gagen D, Fairbairn LJ, Lord BI, Testa NG (1998) CD34 + AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells 16:387–396
Matsumoto K, Yasui K, Yamashita N, Horie Y, Yamada T, Tani Y, Shibata H, Nakano T (2000) In vitro proliferation potential of AC133 positive cells in peripheral blood. Stem Cells 18:196–203
Gordon PR, Leimig T, Babarin-Dorner A, Houston J, Holladay M, Mueller I, Geiger T, Handgretinger R (2003) Large-scale isolation of CD133+ progenitor cells from G-CSF mobilized peripheral blood stem cells. Bone Marrow Transplant 31:17–22
Bühring HJ, Seiffert M, Bock TA, Scheding S, Thiel A, Scheffold A, Kanz L, Brugger W (1999) Expression of novel surface antigens on early hematopoietic cells. Ann N Y Acad Sci 872:25–38, Discussion
Quirici N, Soligo D, Caneva L, Servida F, Bossolasco P, Deliliers GL (2001) Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. Br J Haematol 115:186–194
Bakondi B, Spees JL (2010) Human CD133-derived bone marrow stromal cells establish ectopic hematopoietic microenvironments in immunodeficient mice. Biochem Biophys Res Commun 400:212–218
Pozzobon M, Piccoli M, Ditadi A, Bollini S, Destro R, Destro R, ndre-Schmutz I, Masiero L, Lenzini E, Zanesco L, Petrelli L, Cavazzana-Calvo M, Gazzola MV, De CP (2009) Mesenchymal stromal cells can be derived from bone marrow CD133+ cells: implications for therapy. Stem Cells Dev 18:497–510
Koutna I, Peterkova M, Simara P, Stejskal S, Tesarova L, Kozubek M (2011) Proliferation and differentiation potential of CD133+ and CD34+ populations from the bone marrow and mobilized peripheral blood. Ann Hematol 90:127–137
Bissels U, Wild S, Tomiuk S, Hafner M, Scheel H, Mihailovic A, Choi YH, Tuschl T, Bosio A (2011) Combined characterization of microRNA and mRNA profiles delineates early differentiation pathways of CD133+ and CD34+ hematopoietic stem and progenitor cells. Stem Cells 29:847–857
Boxall SA, Cook GP, Pearce D, Bonnet D, El-Sherbiny YM, Blundell MP, Howe SJ, Leek JP, Markham AF, de Wynter EA (2009) Haematopoietic repopulating activity in human cord blood CD133+ quiescent cells. Bone Marrow Transplant 43:627–635
Hess DA, Wirthlin L, Craft TP, Herrbrich PE, Hohm SA, Lahey R, Eades WC, Creer MH, Nolta JA (2006) Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood 107:2162–2169
Gallacher L, Murdoch B, Wu DM, Karanu FN, Keeney M, Bhatia M (2000) Isolation and characterization of human CD34(−)Lin(−) and CD34(+)Lin(−) hematopoietic stem cells using cell surface markers AC133 and CD7. Blood 95:2813–2820
Kimura T, Asada R, Wang J, Kimura T, Morioka M, Matsui K, Kobayashi K, Henmi K, Imai S, Kita M, Tsuji T, Sasaki Y, Ikehara S, Sonoda Y (2007) Identification of long-term repopulating potential of human cord blood-derived CD34-flt3- severe combined immunodeficiency-repopulating cells by intra-bone marrow injection. Stem Cells 25:1348–1355
Gotze KS, Schiemann M, Marz S, Jacobs VR, Debus G, Peschel C, Oostendorp RA (2007) CD133-enriched CD34(−) (CD33/CD38/CD71)(−) cord blood cells acquire CD34 prior to cell division and hematopoietic activity is exclusively associated with CD34 expression. Exp Hematol 35:1408–1414
Summers YJ, Heyworth CM, de Wynter EA, Hart CA, Chang J, Testa NG (2004) 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 22:704–715
Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, Kotb M, Gillies SD, King M, Mangada J, Greiner DL, Handgretinger R (2005) Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 174:6477–6489
Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130
Drake AC, Khoury M, Leskov I, Iliopoulou BP, Fragoso M, Lodish H, Chen J (2011) Human CD34+ CD133+ hematopoietic stem cells cultured with growth factors including Angptl5 efficiently engraft adult NOD-SCID Il2rgamma−/− (NSG) mice. PLoS One 6:e18382
He X, Gonzalez V, Tsang A, Thompson J, Tsang TC, Harris DT (2005) Differential gene expression profiling of CD34+ CD133+ umbilical cord blood hematopoietic stem progenitor cells. Stem Cells Dev 14:188–198
Hemmoranta H, Hautaniemi S, Niemi J, Nicorici D, Laine J, Yli-Harja O, Partanen J, Jaatinen T (2006) Transcriptional profiling reflects shared and unique characters for CD34+ and CD133+ cells. Stem Cells Dev 15:839–851
Wagner W, Ansorge A, Wirkner U, Eckstein V, Schwager C, Blake J, Miesala K, Selig J, Saffrich R, Ansorge W, Ho AD (2004) Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis. Blood 104:675–686
Murdoch B, Gallacher L, Chadwick K, Bhatia M (2002) Characterization of retroviral gene transfer into highly purified human CD34(−) cells with primitive hematopoietic capacity. Mol Ther 5:635–643
Kuçi S, Wessels JT, Buhring HJ, Schilbach K, Schumm M, Seitz G, Loffler J, Bader P, Schlegel PG, Niethammer D, Handgretinger R (2003) Identification of a novel class of human adherent CD34- stem cells that give rise to SCID-repopulating cells. Blood 101:869–876
Kuçi S, Kuçi Z, Schmid S, Seitz G, Muller I, Dufke A, Leimig T, Murti G, Jurecic R, Schumm M, Lang P, Bruchelt G, Bader P, Klingebiel T, Niethammer D, Handgretinger R (2008) Efficient in vitro generation of adult multipotent cells from mobilized peripheral blood CD133+ cells. Cell Prolif 41:12–27
Handgretinger R, Gordon PR, Leimig T, Chen X, Bühring HJ, Niethammer D, Kuci S (2003) Biology and plasticity of CD133+ hematopoietic stem cells. Ann N Y Acad Sci 996:141–151
Giebel B, Corbeil D, Beckmann J, Hohn J, Freund D, Giesen K, Fischer J, Kogler G, Wernet P (2004) Segregation of lipid raft markers including CD133 in polarized human hematopoietic stem and progenitor cells. Blood 104:2332–2338
Freund D, Oswald J, Feldmann S, Ehninger G, Corbeil D, Bornhäuser M (2006) Comparative analysis of proliferative potential and clonogenicity of MACS-immunomagnetic isolated CD34+ and CD133+ blood stem cells derived from a single donor. Cell Prolif 39:325–332
Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S (2000) Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95:952–958
Salven P, Mustjoki S, Alitalo R, Alitalo K, Rafii S (2003) VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells. Blood 101:168–172
Ciraci E, Della BS, Salvucci O, Rofani C, Segarra M, Bason C, Molinari A, Maric D, Tosato G, Berardi AC (2011) Adult human circulating CD34(−)Lin(−)CD45(−)CD133(−) cells can differentiate into hematopoietic and endothelial cells. Blood 118:2105–2115
Koehl U, Zimmermann S, Esser R, Sorensen J, Gruttner HP, Duchscherer M, Seifried E, Klingebiel T, Schwabe D (2002) Autologous transplantation of CD133 selected hematopoietic progenitor cells in a pediatric patient with relapsed leukemia. Bone Marrow Transplant 29:927–930
Isidori A, Motta MR, Tani M, Terragna C, Zinzani P, Curti A, Rizzi S, Taioli S, Giudice V, D’Addio A, Gugliotta G, Conte R, Baccarani M, Lemoli RM (2007) Positive selection and transplantation of autologous highly purified CD133(+) stem cells in resistant/relapsed chronic lymphocytic leukemia patients results in rapid hematopoietic reconstitution without an adequate leukemic cell purging. Biol Blood Marrow Transplant 13:1224–1232
Feller N, van der Pol MA, Waaijman T, Weijers GW, Westra G, Ossenkoppele GJ, Schuurhuis GJ (2005) Immunologic purging of autologous peripheral blood stem cell products based on CD34 and CD133 expression can be effectively and safely applied in half of the acute myeloid leukemia patients. Clin Cancer Res 11:4793–4801
Lang P, Bader P, Schumm M, Feuchtinger T, Einsele H, Fuhrer M, Weinstock C, Handgretinger R, Kuci S, Martin D, Niethammer D, Greil J (2004) Transplantation of a combination of CD133+ and CD34+ selected progenitor cells from alternative donors. Br J Haematol 124:72–79
Lang P, Schumm M, Greil J, Bader P, Klingebiel T, Muller I, Feuchtinger T, Pfeiffer M, Schlegel PG, Niethammer D, Handgretinger R (2005) A comparison between three graft manipulation methods for haploidentical stem cell transplantation in pediatric patients: preliminary results of a pilot study. Klin Padiatr 217:334–338
Bitan M, Shapira MY, Resnick IB, Zilberman I, Miron S, Samuel S, Ackerstein A, Elad S, Israel S, Amar A, Fibach E, Or R, Slavin S (2005) Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133 + −purified stem cells. Exp Hematol 33:713–718
Bornhäuser M, Eger L, Oelschlaegel U, Auffermann-Gretzinger S, Kiani A, Schetelig J, Illmer T, Schaich M, Corbeil D, Thiede C, Ehninger G (2005) Rapid reconstitution of dendritic cells after allogeneic transplantation of CD133+ selected hematopoietic stem cells. Leukemia 19:161–165
Fargeas CA, Fonseca A-V, Huttner WB, Corbeil D (2006) Prominin-1 (CD133): from progenitor cells to human diseases. Future Lipidol 1:213–225
Fonseca A-V, Bauer N, Corbeil D (2008) The stem cell marker CD133 meets the endosomal compartment – New insights into the cell division of hematopoietic stem cells. Blood Cells Mol Dis 41:194–195
Bauer N, Wilsch-Bräuninger M, Karbanová J, Fonseca AV, Strauss D et al (2011) Haematopoietic stem cell differentiation promotes the release of prominin-1/CD133-containing membrane vesicles-a role of the endocytic-exocytic pathway. EMBO Mol Med 3:398–409
Zacchigna S, Oh H, Wilsch-Bräuninger M, Missol-Kolka E, Jászai J et al (2009) Loss of the cholesterol-binding protein prominin-1/CD133 causes disk dysmorphogenesis and photoreceptor degeneration. J Neurosci 29:2297–2308
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Handgretinger, R., Kuçi, S. (2013). CD133-Positive Hematopoietic Stem Cells: From Biology to Medicine. In: Corbeil, D. (eds) Prominin-1 (CD133): New Insights on Stem & Cancer Stem Cell Biology. Advances in Experimental Medicine and Biology, vol 777. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5894-4_7
Download citation
DOI: https://doi.org/10.1007/978-1-4614-5894-4_7
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-5893-7
Online ISBN: 978-1-4614-5894-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

