Abstract
The complexity of central nervous system (CNS) degenerative/inflammatory diseases and the lack of substantially effective treatments point to the need for a broader therapeutic approach to target multiple components involved in the disease pathogenesis. We suggest a novel approach directed for the elimination of pathogenic agents from the CNS and, in parallel, its enrichment with an array of neuroprotective substances, using a “cerebrospinal fluid (CSF) exchange” procedure, in which endogenous (pathogenic) CSF is removed and replaced by artificial CSF (aCSF) enriched with secretions of human mesenchymal stem cells (MSCs). MSCs produce a variety of neuroprotective agents and have shown beneficial effects when cells are transplanted in animals and patients with CNS diseases. Our data show that MSCs grown in aCSF secrete neurotrophic factors, anti-inflammatory cytokines, and anti-oxidant agents; moreover, MSC-secretions-enriched-aCSF exerts neuroprotective and immunomodulatory effects in neuronal cell lines and spleen lymphocytes. Treatment of experimental-autoimmune-encephalomyelitis (EAE) mice with this enriched-aCSF using an intracerebroventricular (ICV) CSF exchange procedure (“CSF exchange therapy”) caused a significant delay in the onset of EAE and amelioration of the clinical symptoms, paralleled by a reduction in axonal damage and demyelination. These findings point to the therapeutic potential of the CSF exchange therapy using MSC-secretions-enriched-aCSF in inflammatory/degenerative diseases of the CNS.
Highlights
Degenerative diseases of the central nervous system (CNS) affect cognitive and motor functions and are the most common causes of chronic disability in adult life
We present here our results of cerebrospinal fluid (CSF) exchange therapy in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS), in which endogenous CSF was exchanged with artificial CSF (aCSF) enriched with secretions of human mesenchymal stem cells (MSCs)
In this study we present CSF exchange therapy, a novel therapeutic approach aimed at exchanging the endogenous pathogenic CSF with a new and healthy one, through drainage of the endogenous CSF and its continuous replacement with aCSF enriched with secretions of the MSCs
Summary
Degenerative diseases of the central nervous system (CNS) affect cognitive and motor functions and are the most common causes of chronic disability in adult life. Therapy may be more effective if directed to both eliminate the array of pathogenic agents from the CNS and enrich the CNS with an array of protective agents. In this way, the CNS milieu could change from a pathogenic to healthy one. The CSF provides a “sink action” by which the metabolic waste products formed in the nervous tissue during its metabolic activity diffuse rapidly into the CSF and are removed into the bloodstream as CSF is absorbed It provides a metabolic support and an active signaling milieu to the CNS, including the distribution of biologically active substances throughout the brain [2]. Its immediate contact with the brain and its ability to swiftly distribute signals across vast distances in the CNS makes the CSF a suitable route for a therapeutic intervention aiming to change the CNS milieu
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