Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury

Abstract

The therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%. Further histological analyses in CX(3)CR1(EGFP/+) CCR2(RFP/+) transgenic mice indicated that MSC/IL-13 significantly decrease the number of resident microglia and increase the number of alternatively activated macrophages. In addition, the number of macrophage-axon contacts in MSC/IL-13-treated mice was decreased by 50%, suggesting a reduction in axonal dieback. Our data provide evidence that transplantation of MSC/IL-13 leads to improved functional and histopathological recovery in a mouse model of SCI.