Study Of The Treatment Of Multiple Sclerosis By Transplantation Of PMSCs And Intravenous Injection Of Drugs To Ameliorate CNS Micro-environment

Multiple sclerosis(MS)is an autoimmune disease characterized by aberrant activation of immune cells,which causes demyelination,axonal damage,and inflammation in the central nervous system(CNS).Placental derived mesenchymal stem cells(PMSC)have been suggested as a possible source of cells to treat MS due to their immunomodulatory functions,non-invasive access,abundant yield and potential to differentiate into neurons and oligodendrocytes.However,inflammatory cell invasion into grafts negatively impacts the survival and efficacy of transplanted cellsPrevious studies have shown that synthetic C16 peptide can competitively block the transmigration of leukocytes into the CNS,while angiopoietin-1(Ang-1)can inhibit inflammation-induced blood vessel leakage and inflammatory cell infiltration in rats with experimental autoimmune encephalomyelitis(EAE),an animal model of MS.In this study,in order to investigate whether PMSC share similar characteristics with embryonic mesenchymal stem cells(EMSC),and whether transplanted PMSC have the ability to integrate and replace degenerated neural cells,we transplanted rat PMSC and EMSC into the CNS of Lewis rats suffering from EAE.Moreover,we investigated the effects of intravenous administration of C16 and Ang-1 on the efficacy of PMSC transplantation Our findings demonstrated that transplanted PMSC,similar to EMSC,could be effective in decreasing infiltrating inflammatory cells,preserving axons,and ameliorating demyelination,thereby improving the neurological functions of animals.Besides,both PMSC and EMSC had the ability to migrate into inflamed tissues and express neural-glial lineage markers.Compared with the treatments of transplanting PMSC alone,PMSC transplantation accompanied with intravenously administered C16 and Ang-1 was more effective at alleviating demyelination/neuronal loss and neurological dysfunction,reducing inflammatory cell infiltration,perivascular edema and reactive astrogliosis(P<0.05).The following studies revealed that intravenous C16 and Ang-1 improved PMSC engraftment in the CNS and promoted expression of the neurotropic proteins including brain-derived neurotrophic factor(BDNF),growth-associated protein 43(GAP43),p75 neurotrophic receptor as well as the neuronal-glial lineage markers neurofilament protein 200(NF-200)and myelin basic protein(MBP)in the engrafted PMSC.These findings suggested that PMSC may replace EMSC as a source of cells in MS stem cell therapy,and intravenous C16 and angiopoietin-1 could improve the efficacy of PMSC therapy in animal model of MS.