Amelioration of experimental autoimmune encephalomyelitis through transplantation of placental derived mesenchymal stem cells

Hong Jiang,Yuanyuan Zhang,Kewei Tian,Beibei Wang,Shu Han

doi:10.1038/srep41837

Hong Jiang, Yuanyuan Zhang + Show 3 more

Open Access

https://doi.org/10.1038/srep41837

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Journal: Scientific Reports	Publication Date: Feb 10, 2017
Citations: 31	License type: open-access

Affiliation: Sir Run Run Shaw Hospital, Zhejiang University

Abstract

Placental derived mesenchymal stem cells (PMSCs) have been suggested as a possible source of cells to treat multiple sclerosis (MS) due to their immunomodulatory functions, lack of ethical concerns, and potential to differentiate into neurons and oligodendrocytes. To investigate whether PMSCs share similar characteristics with embryonic mesenchymal stem cells (EMSCs), and if transplanted PMSCs have the ability to integrate and replace degenerated neural cells, we transplanted rat PMSCs and EMSCs into the central nervous system (CNS) of Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Our findings demonstrated that transplanted PMSCs, similar to EMSCs, were effective in decreasing infiltrating inflammatory cells, preserving axons, and ameliorating demyelination, thereby improving the neurological functions of animals. Moreover, both PMSCs and EMSCs had the ability to migrate into inflamed tissues and express neural–glial lineage markers. These findings suggest that PMSCs may replace EMSCs as a source of cells in MS stem cell therapy.

Highlights

Inflammatory response associated with Multiple sclerosis (MS) than the classical mouse model by MOG35–55 induction, in which Selim and colleagues have tested and provided some evidence of neuroprotective effects with full-term human placenta (PDMSCs)[16]
We found that expression of transcription factors in inflammatory pathways, such as COX-2 and NF-kB, and inflammatory cytokines, such as TNF-α, IFN-γand IL-2, were all significantly increased in vehicle-treated EAE rats, while Embryonic Stem Cell-Derived Mesenchymal Stem Cells (EMSCs) and PMECs treatments markedly reduced the expression of these factors (Figures S3 and S4)
To test whether EMSCs and PMSCs transplantation ameliorated these pathological changes in EAE rats, we examined the morphological changes of the myelin sheath, blood vessels, and neurons by myelin basic protein (MBP) staining, and transmission electron microscopy

Summary

Introduction

Inflammatory response associated with MS than the classical mouse model by MOG35–55 induction, in which Selim and colleagues have tested and provided some evidence of neuroprotective effects with full-term human placenta (PDMSCs)[16]. To compare the efficiency of EMSCs and PMSCs in treating MS and to test the integrative capacity of transplanted EMSCs and PMSCs, in the present study, we transplanted PMSCs from green fluorescent protein (GFP) transgenic rats into the CNS of EAE rats through bilateral intracerebroventricular (ICV) injections and intrathecal (ITH) injection. Multiple behavioral and neurological evaluations, histological and immunohistochemical staining, enzyme-linked immunosorbent assays (ELISA), Western blotting, electron microscopy (EM), and electrophysiological tests were adopted to assess a variety of parameters, including inflammation, axonal loss, white matter demyelination, neuronal apoptosis, gliosis, expression of pro-inflammatory cytokines, functional recovery of treated EAE rats, as well as the survival, migration, and differentiation of engrafted PESCs and EMSCs in the cerebral cortex and spinal cord of EAE rats

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Results

Conclusion