The effect of transplanted human Wharton’s jelly mesenchymal stem cells treated with IFN-γ on experimental autoimmune encephalomyelitis mice

The Use of Human Mesenchymal Stem Cells as Therapeutic Agents for the in vivo Treatment of Immune-Related Diseases: A Systematic Review

“…Regarding the studies in which hMSCs were used for the treatment of multiple sclerosis ( 102 , 121 – 145 , 154 ), five studies ( 125 , 131 , 132 , 134 , 135 ) were conducted in humans, 19 ( 102 , 121 – 124 , 126 – 129 , 133 , 136 – 139 , 141 , 143 – 145 , 154 ) were conducted in mice and three studies ( 130 , 140 , 142 ) used rats as the experimental model. Among these studies, 16 used hMSCs isolated from the bone marrow ( 102 , 122 , 123 , 125 – 128 , 131 – 137 , 138 , 143 , 154 ), seven isolated hMSCs from the adipose tissue ( 121 , 128 , 130 , 136 , 140 , 141 , 145 ), four isolated hMSCs from the umbilical cord ( 124 , 128 , 142 , 144 ) and two isolated hMSCs from the placenta ( 129 , 139 ). In only one study ( 102 ), hMSCs were obtained from the differentiation of embryonic stem cells.…”

“…In general, the administration of hMSCs reduced the levels of pro-inflammatory cytokines such as IFN-γ ( 122 , 126 , 128 , 130 , 133 , 141 – 144 ), TNF-α ( 122 , 124 , 126 , 128 , 133 , 142 , 154 ), IL-1 ( 124 ), IL-2 ( 122 , 128 ), IL-12 ( 122 ), and IL-17 ( 121 , 122 , 124 , 128 , 130 , 138 , 143 , 144 , 154 ) and increased the levels of anti-inflammatory cytokines such as IL-4 ( 122 , 124 , 126 , 130 , 133 , 138 , 140 , 142 , 143 , 144 ), IL-5 ( 122 ), and IL-10 ( 124 , 126 , 128 , 130 , 133 , 138 , 139 , 141 – 143 ). The level of the pro and anti-inflammatory cytokine IL-6 was found to be increased in some studies ( 128 , 136 ) while in others the level of this cytokine decreased ( 124 , 154 ) after the administration of hMSCs.…”

“…Some of the studies selected also reported positive results when hMSCs were stimulated with inflammatory cytokines prior to their administration for the treatment of immune-related diseases. For instance, a study conducted by Torkaman et al ( 144 ) demonstrated that the administration of umbilical cord-derived hMSCs previously treated with IFN-γ resulted in a higher inhibition in leukocyte infiltration into the central nervous system and in the reduction in the symptoms of experimental autoimmune encephalomyelitis in mice, compared to the administration of untreated umbilical cord-derived hMSCs. Furthermore, administration of umbilical cord-derived hMSCs previously treated with IFN-γ stimulated the clonal expansion of Treg cells and decreased the secretion and gene expression of inflammatory cytokines in experimental autoimmune encephalomyelitis mice.…”

Immunomodulatory Effects of Mesenchymal Stem Cells on T- and B-Cells in a Quiescent State in a Chronic Experimental Model of Autoimmune Encephalomyelitis

“…A potential alternative to neural precursor cells is mesenchymal stem cells (MSC). Recently, the actions exerted by adipose-derived mesenchymal stromal cells, [10][11][12][13][14] placenta-derived mesenchymal stem cells, 15,16 Wharton's jelly mesenchymal stem cells, 17 human decidua-derived mesenchymal stem cells 18 and human umbilical cord blood mesenchymal stromal cells 19 have been reported in experimental autoimmune encephalomyelitis (EAE) animal models.…”

“…These cells could be ideal candidates for application in human diseases, since they offer significant practical advantages: they are obtained from different adult tissues and can readily be cultured and expanded; they are multipotent and self-renewing. They have the capacity to differentiate into mesodermal-derived 20 or into neural-like and glial-like cells 21 ; they have been shown to have immunoregulatory properties 10,[12][13][14]17,18,22,23 ; they secrete factors that may stimulate endogenous neural stem cells in the CNS 24,25 ; they can be safely injected autologously without the need for immunosuppression 26 ; they decrease the number of infiltrating inflammatory cells, preserving axons and ameliorating demyelination, 15,19,27,28 ameliorate neuroinflammation 11,29 and exert a neurotrophic action. 16 All these features make MSC suitable for therapy in autoimmune diseases.…”