title: Functional differences between subpopulations of mobilized peripheral blood-derived CD34+ cells expressing different levels of HLA-DR, CD33, CD38 and c-kit antigens.
abstract: We have investigated the functional characteristics of peripheral blood-derived CD34+ cells mobilized by a combination of chemotherapy and G-CSF (mobilized peripheral blood-derived [MPB] CD34+ cells). In this study, subpopulations of MPB CD34+ cells have been directly compared in clonal cultures, long-term cultures with bone marrow (BM) stromal cells, and single-cell cultures. MPB CD34+ cells could be subdivided by expression levels of HLA-DR (DR), CD38, CD33 and c-kit antigens. The majority of MPB CD34+ cells expressed DR and CD38 antigens. In contrast, approximately 60% and 20% of the MPB CD34+ cells expressed CD33 and c-kit antigens, respectively. Interestingly, MPB CD34+ cells can be subdivided into three fractions which express high, low or negative levels of c-kit receptor. All types of committed progenitors were observed in populations of CD34+DR+, CD34+DR-, CD34+CD33-, CD34+CD38+ and CD34+ c-kit(low) cells. Colony forming unit-granulocyte/macrophage was highly enriched in the population of CD34+CD33+ cells, whereas BFU-E was highly enriched in the population of CD34+ c-kit(high) cells. In the population of CD34+CD38- cells, however, a few myeloid progenitors were detected. In addition, limiting dilution analyses clearly showed that the long-term culture-initiating cell (LTC-IC) is enriched in the populations of CD34+DR-, CD34+CD33- and CD34+c-kit-(or low) cells, but very few in CD34+ c-kit(high) cells, and that CD38 antigen is not a useful marker for the enrichment of LTC-IC derived from MPB CD34+ cells. Moreover, single cell clone sorting experiments clearly demonstrated the functional differences between CD34+CD38+ and CD34+CD38- cells as well as CD34+ cells expressing different levels of c-kit receptor. Our results suggest that an immunophenotype of LTC-IC is different between BM-, cord blood- and MPB-derived CD34+ cells and that primitive and committed progenitors existing in these sources may be functionally different.
authors.affiliation: Second Department of Internal Medicine, Shiga University of Medical Science, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakabe
authors.forename: Y
authors.initials: Y
authors.lastname: Ohmizono
authors.forename: S
authors.initials: S
authors.lastname: Tanimukai
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: K J
authors.initials: KJ
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: Y
authors.initials: Y
authors.lastname: Sonoda
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000032:analysis*; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D002455:Cell Division; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology; D002999:Clone Cells / Q000166:cytology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000145:classification* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000166:cytology; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D063268:Sialic Acid Binding Ig-like Lectin 3; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D019009:Proto-Oncogene Proteins c-kit; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1