Abstract
Mesenchymal stem cells (MSCs) are non-haematopoeitic, stromal cells that are capable of differentiating into mesenchymal tissues such as bone and cartilage. They are rare in bone marrow, but have the ability to expand many-fold in culture, and retain their growth and multi-lineage potential. The properties of MSCs make them ideal candidates for tissue engineering. It has been shown that MSCs, when transplanted systemically, can home to sites of injury, suggesting that MSCs possess migratory capacity; however, mechanisms underlying migration of these cells remain unclear. Chemokine receptors and their ligands play an important role in tissue-specific homing of leukocytes. Here we define the cell surface chemokine receptor repertoire of murine MSCs from bone marrow, with a view to determining their migratory activity. We also define the chemokine receptor repertoire of human MSCs from bone marrow as a comparison. We isolated murine MSCs from the long bones of Balb/c mice by density gradient centrifugation and adherent cell culture. Human MSCs were isolated from the bone marrow of patients undergoing hip replacement by density gradient centrifugation and adherent cell culture. The expression of chemokine receptors on the surface of MSCs was studied using flow cytometry. Primary murine MSCs expressed CCR6, CCR9, CXCR3 and CXCR6 on a large proportion of cells (73±11%, 44±25%, 55±18% and 96±2% respectively). Chemotaxis assays were used to verify functionality of these chemokine receptors. We have also demonstrated expression of these receptors on human MSCs, revealing some similarity in chemokine receptor expression between the two species. Consequently, these murine MSCs would be a useful model to further study the role of chemokine receptors in in vivo models of disease and injury, for example in recruitment of MSCs to inflamed tissues for repair or immunosupression.
Highlights
Mesenchymal stem cells (MSCs) are non-haematopoeitic, stromal cells that are capable of differentiating into, and contribute to the regeneration of, mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, adipose and stroma [1,2]
We have demonstrated the functional presence of chemokine receptors on murine MSCs, and have shown that their expression profile exhibits similarities to that of human MSCs
Many recent studies have reported the functional expression of various different chemokine receptors on human MSCs [17,18,19,20,21,22]; Figure 2
Summary
Mesenchymal stem cells (MSCs) are non-haematopoeitic, stromal cells that are capable of differentiating into, and contribute to the regeneration of, mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, adipose and stroma [1,2]. The cell surface expression of chemokine receptors (CCR3-9 and CXCR2-6) was assessed in primary murine MSC cultures at passages 7–9 by flow cytometry (Figure 2) as described. The cell surface expression of chemokine receptors (CCR1-10 and CXCR1-6) was assessed in primary human MSC cultures by flow cytometry, it was found that the trypsin used to remove cells from the flask was removing a large proportion of chemokine receptors from the surface of the cells. A high percentage of both the primary murine MSCs and the C3H/10T1/2 cells were shown to express CXCR6 on the cell surface (9662% and 9861% respectively) (Figure 2); interestingly, this chemokine receptor was expressed on a high proportion (9561%) of human bone-marrow-derived MSCs (Figure 3). The chemokines CXCL16, CXCL9, CCL20 and CCL25 all induced significant migration of murine MSCs in a dosedependent manner compared to media alone (Figure 4), whereas CXCL12 did not induce migration, indicating that the receptors detected on these cells by flow cytometry are functional
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