Treatment of the bone marrow stromal stem cell supernatant by nasal administration\u2014a new approach to EAE therapy

Xi Wang,Siying Qu,Zhongze He,Hulun Li,Wei Zhao,Bo Sun,Wantong Zhai,Shenyue Wang,Zhaoying Li,Jiahui Zhu,Lingyang Wang,Xiaoyi Zou

doi:10.1186/s13287-019-1423-6

Abstract

IntroductionMultiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS). CNS has its own unique structural and functional features, while the lack of precision regulatory element with high specificity as therapeutic targets makes the development of disease treatment in the bottleneck. Recently, the immunomodulation and neuroprotection capabilities of bone marrow stromal stem cells (BMSCs) were shown in experimental autoimmune encephalomyelitis (EAE). However, the administration route and the safety evaluation limit the application of BMSC. In this study, we investigated the therapeutic effect of BMSC supernatant by nasal administration.MethodsIn the basis of the establishment of the EAE model, the BMSC supernatant were treated by nasal administration. The clinical score and weight were used to determine the therapeutic effect. The demyelination of the spinal cord was detected by LFB staining. ELISA was used to detect the expression of inflammatory factors in serum of peripheral blood. Flow cytometry was performed to detect pro-inflammatory cells in the spleen and draining lymph nodes.ResultsBMSC supernatant by nasal administration can alleviate B cell-mediated clinical symptoms of EAE, decrease the degree of demyelination, and reduce the inflammatory cells infiltrated into the central nervous system; lessen the antibody titer in peripheral bloods; and significantly lower the expression of inflammatory factors. As a new, non-invasive treatment, there are no differences in the therapeutic effects between BMSC supernatant treated by nasal route and the conventional applications, i.e. intraperitoneal or intravenous injection.ConclusionsBMSC supernatant administered via the nasal cavity provide new sights and new ways for the EAE therapy.

Highlights

Multiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS)
bone marrow stromal stem cells (BMSCs) supernatant by nasal administration can alleviate B cell-mediated clinical symptoms of EAE, decrease the degree of demyelination, and reduce the inflammatory cells infiltrated into the central nervous system; lessen the antibody titer in peripheral bloods; and significantly lower the expression of inflammatory factors
We found that after intranasal administration of BMSC supernatant, the day when the EAE onset was Effects of BMSC supernatant treatment on demyelination of the spinal cord and central nervous system The demyelination of the spinal cord and the inflammatory infiltration of the CNS can reflect the severity of EAE

Summary

Introduction

Multiple sclerosis (MS) is one of the most common autoimmune diseases of the central nervous system (CNS). The immunomodulation and neuroprotection capabilities of bone marrow stromal stem cells (BMSCs) were shown in experimental autoimmune encephalomyelitis (EAE). Multiple sclerosis is a common debilitating disease of the central nervous system that is long believed to be of an autoimmune origin [1]. Experimental studies in animals have reported that BMSCs can ameliorate neurologic deficits and facilitate functional recovery in many disorders of the central nervous system, such as Parkinson’s disease [18], traumatic brain injury [19], spinal cord injury [20, 21], multiple sclerosis [22], and cerebral ischemia [23]. Many studies focused on BMSCs’ ability to secrete a series of bioactive molecules, as cytokines and growth factors in response to diseases [26,27,28]

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