Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway.

Mesenchymal stem cells (MSCs) are multipotent cells that can skew the balance of M1/M2 macrophage polarization towards the M2 phenotype via their paracrine effects, thereby promoting anatomical and functional recovery after many inflammatory diseases induced by macrophages. However, the underlying mechanism is still poorly understood. This study focused on the IL-10/STAT3 pathway and investigated whether IL-10 secreted by PBMSCs could mediate M2 polarization through the activation of this pathway. In this study, a Transwell system was used for coculturing macrophages and PBMSCs. ELISA and RT-qPCR analysis found that PBMSCs and their conditioned media (P-CM) significantly induced the expression of IL-10, while significantly inhibiting the expression of IL-1ß and TNF-α; moreover, this effect could be reversed by adding Ab9969 (an IL-10 neutralizing antibody) and Stattic (a STAT3 inhibitor). Furthermore, western blotting and immunofluorescence assays demonstrated that JAK1/STAT3 signaling was significantly upregulated in macrophages cocultured with PBMSCs or P-CM, accompanied by an increase in the M2 biomarker CD206 and a decrease in the M1 biomarker CD86. This effect could also be reversed by blocking the IL-10/STAT3 pathway with Ab9969 and Stattic. In summary, PBMSCs could mediate the polarization of M2 macrophages by activating the IL-10/STAT3 pathway.

Effects of astrocytes and microglia on neuroinflammation after spinal cord injury and related immunomodulatory strategies.

Spinal cord injury (SCI) is a catastrophic event which is still without adequate therapies. Neuroinflammation is the main pathogenesis of secondary damage post-SCI, leading to tissue loss and neurological dysfunction. Previous studies have shown that microglia and astrocytes are the major immune cells in the central nervous system (CNS) and play a crucial role in modulating neuroinflammatory responses. In this study, we mainly review the effects of neuroinflammation in SCI, focusing on the contributions of microglia and astrocytes and their cross-talk. Furthermore, we will also discuss therapeutic strategies on how to regulate their immunophenotype to suppress robust inflammation and facilitate injury prognosis.

Neuroinflammation and Scarring After Spinal Cord Injury: Therapeutic Roles of MSCs on Inflammation and Glial Scar.

Transected axons are unable to regenerate after spinal cord injury (SCI). Glial scar is thought to be responsible for this failure. Regulating the formation of glial scar post-SCI may contribute to axonal regrow. Over the past few decades, studies have found that the interaction between immune cells at the damaged site results in a robust and persistent inflammatory response. Current therapy strategies focus primarily on the inhibition of subacute and chronic neuroinflammation after the acute inflammatory response was executed. Growing evidences have documented that mesenchymal stem cells (MSCs) engraftment can be served as a promising cell therapy for SCI. Numerous studies have shown that MSCs transplantation can inhibit the excessive glial scar formation as well as inflammatory response, thereby facilitating the anatomical and functional recovery. Here, we will review the effects of inflammatory response and glial scar formation in spinal cord injury and repair. The role of MSCs in regulating neuroinflammation and glial scar formation after SCI will be reviewed as well.