Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury

Abstract

Various immune cells and cytokines are present in the aftermath of peripheral nerve injuries (PNI), and coordination of the local inflammatory response is of great significance for the recovery of PNI. Mesenchymal stem cells (MSCs) exhibit immunosuppressive and anti-inflammatory abilities which can accelerate tissue regeneration and attenuate inflammation, but the role of MSCs in the regulation of the local inflammatory microenvironment after PNI has not been widely studied. Here, we summarize the known interactions between MSCs, immune cells, and inflammatory cytokines following PNI with a focus on the immunosuppressive role of MSCs. We also discuss the immunomodulatory potential of MSC-derived extracellular vesicles as a new cell-free treatment for PNI.

Implantation of a nerve protector embedded with human GMSC-derived Schwann-like cells accelerates regeneration of crush-injured rat sciatic nerves

“…They found a significantly higher infiltration of M2 macrophages in response to the SIS Axoguard conduits but a predominant infiltration of M1 macrophages in response to the NeuraGen Nerve Guide conduits [ 70 ]. In addition to immunomodulatory biomaterials, it is well known that MSCs of different tissue origins can potently promote pro-regenerative (M2) macrophage polarization while inhibiting pro-inflammatory (M1) macrophage activation both in vitro and in various preclinical disease models [ 14 ]. MSCs exert their therapeutic effects on PNI possibly through their dual functions, multipotent differentiation capacity into neural type of cells and their paracrine secretion of an array of bioactive factors with multiple trophic effects on both neural and nonneural cells [ 13 ], whereby the potent immunomodulatory effects of MSCs on immune cells, particularly macrophages, may constitute one of the major mechanisms by which MSCs exert their therapeutic effects on PNI [ 14 ].…”

“…In addition to immunomodulatory biomaterials, it is well known that MSCs of different tissue origins can potently promote pro-regenerative (M2) macrophage polarization while inhibiting pro-inflammatory (M1) macrophage activation both in vitro and in various preclinical disease models [ 14 ]. MSCs exert their therapeutic effects on PNI possibly through their dual functions, multipotent differentiation capacity into neural type of cells and their paracrine secretion of an array of bioactive factors with multiple trophic effects on both neural and nonneural cells [ 13 ], whereby the potent immunomodulatory effects of MSCs on immune cells, particularly macrophages, may constitute one of the major mechanisms by which MSCs exert their therapeutic effects on PNI [ 14 ]. Our previous studies showed that GMSCs possess potent immunomodulatory effects on pro-inflammatory (M1)/pro-regenerative (M2) macrophages both in vitro and in mice skin wound models [ 39 ].…”

“…In recent years, much progress has been made in fabricating functionalized nerve guidance conduits loaded with different types of bioactive noncellular or cellular components, particularly the combination with multipotent mesenchymal stem cells (MSCs) of different tissue origins, including dental tissues [ 12 , 13 ]. Accumulating evidence has shown that MSC-based tissue engineering and regenerative therapy holds great promise to promote nerve regeneration because of the potent immunomodulatory/anti-inflammatory functions and multifaced trophic effects of MSCs, such as neurotrophic or neuroprotective, pro-angiogenic, antioxidant, and anti-fibrotic effects due to their paracrine secretion of a myriad of biological factors [ 13 , 14 ]. Interestingly, a unique population of MSCs has been identified and isolated from several neural crest (NC)-derived postnatal tissues, such as dental pulp [ 15 ], oral mucosa/gingiva [ 16 – 18 ], and skin epidermis [ 19 ].…”

Mesenchymal Stromal Cells Preconditioning: A New Strategy to Improve Neuroprotective Properties

“…MSCs can be considered as interesting candidates to develop new therapeutic approaches to counteract ND thanks to these properties, together with the immunomodulatory capacity and the possibility to be isolated by autologous and allogeneic sources [26,31,32].…”

MSC-ACE2 Ameliorates Streptococcus uberis-Induced Inflammatory Injury in Mammary Epithelial Cells by Upregulating the IL-10/STAT3/SOCS3 Pathway

“…Mesenchymal stem cells are pluripotent stem cells with multiple biological potentials, such as regeneration, immunomodulation, repair of damaged tissues, home to the site of injury, and other properties ( 11 – 13 ). Currently, mesenchymal stem cell (MSC) treatment positively affects diseases.…”