Muse cells decrease the neuroinflammatory response by modulating the proportion of M1 and M2 microglia in vitro.

Neuroinflammation hinders repair of the central nervous system (CNS). Stem cell transplantation is a very promising approach for treatment of CNS injuries. However, it is difficult to select seed cells that can both facilitate nerve regeneration and improve the microenvironment in the CNS. In this study, we isolated multilineage-differentiating stress-enduring (Muse) cells from bone marrow mesenchymal stem cells. We explored the anti-inflammatory effect and mechanism of Muse cells in vitro by coculture of Muse cells with lipopolysaccharide-stimulated microglia. Our results showed that Muse cells effectively reduced the transcription and secretion of tumor necrosis factor α and interleukin-1ß and increased the expression of transforming growth factor-ß and interleukin-10 in microglia. In addition, Muse cells decreased the number of M1 microglia and increased the proportion of M2 microglia in an inflammatory environment more effectively than bone marrow mesenchymal stem cells. We also show that Muse cells inhibited the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and inhibited the expression of the phosphorylated forms of transcription factor p65, nuclear factor (NF)-κB inhibitor alpha, and p38 mitogen-activated protein kinase (MAPK) in microglia. Therefore, we suggest Muse cells cause antineuroinflammatory effects by inhibition of the TLR4/MyD88/NF-κB and p38 MAPK signaling pathways in microglia. Our results shed light on the function of Muse cells in relation to CNS diseases and provide insight into the selection of seed cells.

Human Muse cells-derived neural precursor cells as the novel seed cells for the repair of spinal cord injury.

At present, stem cell transplantation has a significant therapeutic effect on spinal cord injury (SCI), however, it is still challenging for the seed cells selection. In this study, in order to explore cells with wide neural repair potentials, we selected the pluripotent stem cells multilineage-differentiating stress-enduring (Muse) cells, inducing the in vitro differentiation of human Muse cells into neural precursor cells (Muse-NPCs) by applying neural induction medium. Here, we found induced Muse-NPCs expressed neural stem cell markers Nestin and NCAM, capable of differentiating into three types of neural cells (neuron, astrocyte and oligodendrocyte), and have certain biological functions. When Muse-NPCs were transplanted into rats suffering from T10 SCI, motor function was improved. These results provide an insight for application of Muse-NPCs in cell therapy or tissue engineering for the repair of SCI in future.