Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1.
Murine IgM monoclonal antibody STRO-1 identifies a cell surface antigen expressed by stromal elements in human bone marrow (BM). STRO-1 binds to approximately 10% of BM mononuclear cells, greater than 95% of which are nucleated erythroid precursors, but does not react with committed progenitor cells (colony-forming unit granulocyte-macrophage [CFU-GM], erythroid bursts [BFU-E], and mixed colonies [CFU-Mix]). Fibroblast colony-forming cells (CFU-F) are present exclusively in the STRO-1+ population. Dual-color cell sorting using STRO-1 in combination with antibody to glycophorin A yields a population approximately 100-fold enriched in CFU-F in the STRO-1+/glycophorin A- population. When plated under long-term BM culture (LTBMC) conditions, STRO-1+ cells generate adherent cell layers containing multiple stromal cell types, including adipocytes, smooth muscle cells, and fibroblastic elements. STRO-1+ cells isolated from LTBMC at later times retain the capacity to generate adherent layers with a cellular composition identical to that of the parent cultures. The STRO-1-selected adherent layers are able to support the generation of clonogenic cells and mature hematopoietic cells from a population of CD34+ cells highly enriched in so-called long-term culture-initiating cells. We conclude that antibody STRO-1 binds to BM stromal elements with the capacity to transfer the hematopoietic microenvironment in vitro.
Simmons
P J
PJ
Department of Medical Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Torok-Storb
B
B
D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007938:Leukemia / Q000276:immunology / Q000473:pathology; D009130:Muscle, Smooth / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M