We previously reported the purification, culture-expansion, and osteogenic differentiation potential of mesenchymal progenitor cells (MPCs) derived from human bone marrow. As a first step to establishing the phenotypic characteristics of MPCs, we reported on the identification of unique cell surface proteins which were detected with monoclonal antibodies. In this study, the phenotypic characterization of human marrow-derived MPCs is further established through the identification of a cytokine expression profile under standardized growth medium conditions and in the presence of regulators of the osteogenic and stromal cell lineages, dexamethasone and interleukin-1 a (IL-1 a), respectively. Constitutively expressed cytokines in this growth phase include G-CSF, SCF, LIF, M-CSF, IL-6, and IL-1 1, while GM-CSF, IL-3, TGF-P2, and OSM were not detected in the growth medium. Exposure of cells in growth medium to dexamethasone resulted in a decrease in the expression of LIF, IL-6, and IL-1 1. These cytokines have been reported to exert influence on the differentiation of cells derived from the bone marrow stroma through target cell receptors that utilize gpl30-associated signal transduction pathways. Dexamethasone had no effect on the other cytokines expressed under growth medium conditions and was not observed to increase the expression of any of the cytokines measured in this study. In contrast, IL-1 a increased the expression of G-CSF, M-CSF, LIF, IL-6, and IL-1 1 and induced the expression of GM-CSF. IL-la had no effect on SCF expression and was not observed to decrease the production of any of the cytokines assayed. These data indicate that MPCs exhibit a distinct cytokine expression profile. We interpret this cytokine profile to suggest that MPCs serve specific supportive functions in the microenvironment of bone marrow. MPCs provide inductive and regulatory information which are consistent with the ability to support hematopoiesis, and also supply autocrine, paracrine, and juxtacrine factors that influence the cells of the marrow microenvironment itself. In addition, the cytokine profiles expressed by MPCs, in response to dexamethasone and IL-la, identify specific cytokines whose levels of expression change as MPCs differentiate or modulate their phenotype during osteogenic or stromagenic lineage entrance/progression. 0 1996 Wiley-Liss, Inc.
Bone marrow stroma i s a multi-functional connective tissue composed of a heterogeneous population of cells.
The stroma provides the microenvironment that controls the process of hematopoiesis . Cells of the marrow stroma provide signals to the hematopoietic stem cell and i t s progeny through a variety of molecular mechanisms, including direct cell-cell interactions, secreted soluble bioactive factors, and cell-matrix interactions. In addition, cells from bone marrow stroma have been reported to include u ndifferentiated cells of mesenchymal origin which have the potential to differentiate into multiple phenotypes, including chondrocytes, osteoblasts, adipocytes, stro-ma1 fibroblasts, and potentially other mesenchymal