AC133, A NOVEL MARKER FOR HUMAN HEMATOPOIETIC STEM AND PROGENITOR CELLS

AC133 is one of a new panel of murine hybridoma lines producing monocl onal IgG antibodies (mAbs) to a novel stem cell glycoprotein antigen w ith a molecular weight of 120 kD. AC133 antigen is selectively express ed on Cd34(bright) hematopoietic stem and progenitor cells (progenitor 's) derived from human fetal liver and bone marrow, add blood. It is: not detectable on other blood cells, cultured human umbilical vein end othelial cells (HUVECs), fibroblast cell lines, or the myeloid leukemi a cell line KG1a by standard flow cytometric procedures. All of the no ncommitted CD34(+) cell population, as well as the majority of CD34(+) cells committed to the granulocytic/monocytic pathway. are stained wi th AC133 antibody. In vitro clonogenicity assays have demonstrated tha t the CD34(+)AC133(+) double-positive population from adult bone marro w contains the majority of the CFU-GM, a proportion of the CFU-Mix, an d a minor population of BFU-E. The CD34(dim) and AC133(-) population h as been shown to contain the remaining progenitor cells. AC133-selecte d cells engraft successfully in a fetal sheep transplantation model, a nd human cells harvested from chimeric fetal sheep bone marrow have be en shown to successfully engraft secondary recipients, providing evide nce for the long-term repopulating potential of AC133(+) cells. A cDNA coding for AC133 antigen has been isolated, which codes for a polypep tide consisting of 865 amino acids (aa) with a predicted site of 97 kD . This antigen is modeled as a 5-transmembrane molecule, a structure t hat is novel among known cell surface structures. AC133 antibody provi des an alternative to CD34 for the selection and characterization of c ells necessary for with short- and long-term engraftment, in transplan t situations, for studies of ex vivo expansion strategies, and for gen e therapy. (C) 1997 by The American Society of Hematology.