Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages

Human mesenchymal stem cells (MSCs), bone marrow-derived pluripotent adhere nt cells of mesenchymal origin can differentiate along the osteogenic, chon drogenic, adipogenic, and tendonogenic lineages. In this report we characte rize cytokine and growth factor gene expression by MSCs and investigate the modulation of cytokine expression that occurs during osteogenic and stroma l differentiation. MSCs constitutively expressed mRNA for interleukin (IL)- 6, IL-11, leukemia inhibitory factor (LIF), macrophage colony-stimulating f actor (M-CSF), and stem cell factor (SCF). MSCs treated with IL-1 alpha upr egulated mRNA levels of IL-6, IL-11, and LIF, and began to express detectab le levels of granulocyte colony-stimulating factor (G-CSF), granulocyte mac rophage colony-stimulating factor (GM-CSF). mRNA levels of M-CSF and SCF di d not change. MSCs cultured in osteogenic medium differentiated along the o steogenic lineage and downregulated mRNA levels of IL-6, IL-11 and LIF wher eas, M-CSF and SCF expression were unchanged and G-CSF and GM-CSF remained undetectable. IL-3 was not detected in MSC culture under any conditions. MS Cs precultured in control medium, IL-1 alpha, or osteogenic medium maintain ed similar capacity to support long-term culture initiating cell (LT-CIC). Thus, primary and osteogenic differentiated MSCs produce important hematopo ietic cytokines and support hematopoiesis in long-term cultures, suggesting that these cells may provide an excellent ex vivo environment for hematopo iesis during progenitor cell expansion and mag be important for in vivo cel l therapy.