Human bone marrow stromal cell: Coexpression of markers specific for multiple mesenchymal cell lineages

The role of hematopoietic stem cells in blood cell development is reasonabl y understood, whereas the identity and the function of bone marrow stromal cells are much less clear. Using stromal cells in bone marrow cultures of t he Dexter type, a favorite medium for the study of hematopoiesis, we show t hat stromal cells actually represent a unique cell type. Conventional wisdo m has held that stromal cells in Dexter cultures comprise a mixture of macr ophages, hematopoietic cells, adipocytes, osteoblasts, fibroblasts, muscle cells, and endothelial cells. Our findings demonstrate that Dexter cultures consist of three cell types: macrophages (similar to 35%), hematopoietic c ells (similar to 5%), and nonhematopoietic cells (similar to 60%). Pie have purified the nonhematopoietic cells free of macrophages and hematopoietic cells to produce compelling evidence that they in fact represent a single c ell type (multidifferentiated mesenchymal progenitor cell, MPG) which coexp resses genes specific for various mesenchymal cell lineages including adipo cytes, osteoblasts, fibroblasts, and muscle cells. We further show that the se multi- or pluridifferentiated MPCs are capable of supporting hematopoies is by demonstrating the expression of several hematopoietic growth factors and extracellular matrix receptors including G-CSF, SCF, VCAM-1, ICAM-1, an d ALCAM. Since the MPCs can be easily purified to near homogeneity (95%), t hey can be of value in enhancing engraftment of hematopoietic stem cells. A lso, this new understanding of bone marrow stromal cells as "one cell with many different faces" promises to advance our knowledge of regulatory cellu lar interactions within bone marrow. (C) 2000 Academic Press.