| (Part one) Marrow stromal cells (MSCs), transplanted intravascularly, were shown to be able to migrate into sites of brain injuries, suggesting that MSCs possess migratory capacity. However, the mechanisms underlying the migration of these cells remain unclear. This study sought to explore the roles of some chemokines and their receptors in the trafficking MSCs migration. It has been found that MSCs express CCR2 and CXCR4, the respective receptors for monocyte chemoattratant protein-1 (MCP-1) and stromal cell derived factor-1 (SDF-1), and other chemokine receptors, CX3CR1 and CCR5 using immunofluorescence and RT-PCR. Furthermore, in vitro analysis revealed that recombinant MCP-1 and recombinant SDF-1 induced the migration of MSCs in a G-protein-dependent manner. Intravenously injected MSCs migrated to the lesion site of completely transected spinal cord where RNA of MCP-1 and SDF-1 were assay to be increased after spinal cord injury, suggesting that the MSCs migration may attribute to the increase of MCP-1 and SDF-1. Although this study provided an important insight into the understanding of the mechanisms governing the migration of transplanted MSCs, the change of chemokines after spinal cord injury and the relationship between chemokines and MSCs need to be further explored.(Part two) Although previous studies have indicated that transplantion of MSCs has enhanced axonal sprouting and promoted functional recovery to animals with spinal cord injury, the sequentialevents especially at the cellular level at the lesion site following the transplantation of MSCs have remained elusive. By immunofluorescence and immunoelectron microscopy, this study sought to elucidate their possible roles in promoting axonal sprouting following their transplantation into a completely transected spinal cord. Only a few MSCs were detected in the lesion site at 8w after transplantation, yet there were robust growths of axons.The scarcity of surviving MSCs may be attributed to adverse conditions in their ambient environment. In this connection, the immediate accumulation of large numbers of macrophages/reactive microglias and subsequent cavitation of tissues may be detrimental to their survival. An unexpected finding following MSCs transplantation was the marked increase in numbers of nestin-, GFAP-, NF200-, 01ig3- and CNP-positive cells in the lesion site. By immunoelectron microscopy, CNP cells that were oval or fibroblsst-like formed multiple perineurial-like compartments with their long extending filopodia; more than a score of axons and associated Schwann cells were delineated in each compartment. The spatial relation between Schwann cells and axons were typical of that observed in the peripheral nervous system; rarely were Schwann cells immunostained for CNP. While most CNP cells were fibroblast-like, some showed features of neurons, astrocytes, oligodendrocytes and expressed their respective markers, suggesting their multipotentiality and diverse functions in axonal regeneration. At 1 and 2 weeks after spinal cord injury, a large number of BrdU-positive cells have been shown in the regions of dorsal funiculus and peripheral nerves and the CNP cells were also BrdU-positive, suggesting that the CNP cells were derived from above regions and were multipotentiality. The present results suggest that transplantation of MSCs has elicited the influx and survival of local cells including CNP positive cells and Schwann cells into the site of lesion. These would provide structural support to regenerating axons andpromote their remyelination in spinal cord injury. |
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