Abstract
BackgroundTransplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA) is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored.ResultsWe transplanted green fluorescent protein (GFP) expressed OPCs (GFP-OPCs) into injured spinal cords of rats treated with or without CsA (10 mg/kg). Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI).ConclusionsThese results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.
Highlights
Transplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases
Effect of OPC transplantation and Cyclosporin A (CsA) on infiltration of CD3+T cells and activation of resident microglia cells and/ or macrophages derived from infiltrating monocytes in the injured spinal cords To observe the effect of CsA on immune responses, we examined the infiltration of CD3+T cells, and activation of resident microglia and/or macrophages derived from infiltrating monocytes in the injured spinal cord at 2 weeks after cell transplantation
No statistically significant difference was found in BBB scores between the OPC transplantation groups and the corresponding controls (p > 0.05). These results indicate that the OPC transplantation alone dose not affect the behavior of spinal cord injury (SCI) rats and that CsA-treatment can exert some protective effects leading to functional recovery in SCI rats
Summary
Transplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases. The effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored. At least a part of the functional deficit after spinal cord injury (SCI) is attributable to chronic progressive demyelination [3]. It seems to be an effective strategy to increase the extent of remyelination by transplanting CNS myelin-forming cells into the injured spinal cord. Our study revealed that after being transplanted into the spinal cord, only a small number of the OPCs could survive, and most of them differentiated into astrocytes, but not oligodendrocytes. The mechanisms which caused to this result may be related to a disadvantageous micro-environment in the injured zone created by lipid peroxidation [8,9,10,11], an inflammatory reaction [12,13], and/or an immune response against grafts [5,14,15], etc
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