MESENCHYMAL STEM-CELL SURFACE-ANTIGEN SB-10 CORRESPONDS TO ACTIVATED LEUKOCYTE CELL-ADHESION MOLECULE AND IS INVOLVED IN OSTEOGENIC DIFFERENTIATION

Bone marrow contains a rare population of mesenchymal stem cells (MSCs ) capable of giving rise to multiple mesodermal tissues including bone , cartilage, tendon, muscle, and fat. The cell surface antigen recogni zed by monoclonal antibody SB-10 is expressed on human MSCs but is los t during their developmental progression into differentiated phenotype s. Here we report on the immunopurification of the SB-10 antigen and i ts identification as activated leukocyte-cell adhesion molecule (ALCAM ). Mass spectrometry establishes that the molecular mass of ALCAM is 8 0,303 +/- 193 Da and that it possesses 17,763 +/- 237 Da of N-linked o ligosaccharide substituents. Molecular cloning of a full-length cDNA f rom a MSC expression library demonstrates nucleotide sequence identity with ALCAM. We also identified ALCAM homologs in rat, rabbit, and can ine MSCs, each of which is over 90% identical to human ALCAM in their peptide sequence. The addition of antibody SB-10 F-ab fragments to hum an MSCs undergoing osteogenic differentiation in vitro accelerated the process, thereby implicating a role for ALCAM during bone morphogenes is and adding ALCAM to the group of cell adhesion molecules involved i n osteogenesis. Together, these results provide evidence that ALCAM pl ays a critical role in the differentiation of mesenchymal tissues in m ultiple species across the phylogenetic tree.