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

Abstract

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.

Unleashing Natural Killer Cells in the Tumor Microenvironment–The Next Generation of Immunotherapy?

“…Though additional study is required to test the effect of 293C3-SDIE against physiological solid tumors, this treatment may have important significance for NK cells against the CD133 tumor antigen, which is implicated in multiple cancer types (246). It would be interesting to follow effects of this antibody in future clinical settings, to validate efficacy and the lack of off-target toxicity against healthy cells expressing CD133, such as healthy hematopoietic progenitor cells and others (246,247).…”

Nomenclature of prominin‐1 (CD133) splice variants – an update

“…This nomenclature seems to be generally accepted in the field (5–9), but the rationale underlying it may remain unclear as the rhesus prominin‐1 splice variant described by Husain et al does not correspond to the s1 splice variant (1), and several unpublished human prominin‐1 splice variants appear in the NCBI GenBank database (accession numbers AY449690 to AY449693) with the incorrect suffix according to this same nomenclature. Given the wide use of prominin‐1 (also termed CD133) for the characterization of stem and progenitor cell populations in different normal tissues (10–13) as well as in cancers [(14–16); for review, see (17)], it is important to clarify the rationale of this nomenclature. We believe that it is essential to maintain a consistent designation with regard to potential cross‐specificity toward particular epitopes, e.g.…”

Early neutrophil engraftment following autologous BMT provides a functional predictor of long‐term hematopoietic reconstitution

“…Cells that express CD34 antigen are highly heterogeneous, and a variety of cells that have limited self‐renewal capacity continue to express this antigen. Many additional markers have therefore been used in conjunction with CD34 to characterize hematopoietic stem cells at various stages of differentiation and with different levels of lineage commitment 11‐13 . There is also substantial evidence that at least some hematopoietic stem cells do not express CD34 14,15 …”