Effect of Multiple Sclerosis Cerebrospinal Fluid and Oligodendroglia Cell Line Environment on Human Wharton's Jelly Mesenchymal Stem Cells Secretome.

Karolina Salwierak-Głośna,Mariola Świderek-Matysiak,Małgorzata Domowicz,Paweł Piątek

doi:10.3390/ijms23042177

Karolina Salwierak-Głośna, Mariola Świderek-Matysiak + Show 2 more

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https://doi.org/10.3390/ijms23042177

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Abstract

Multiple sclerosis (MS) is a neurological disorder of autoimmune aetiology. Experimental therapies with the use of mesenchymal stem cells (MSCs) have emerged as a response to the unmet need for new treatment options. The unique immunomodulatory features of stem cells obtained from Wharton’s jelly (WJ-MSCs) make them an interesting research and therapeutic model. Most WJ-MSCs transplants for multiple sclerosis use intrathecal administration. We studied the effect of cerebrospinal fluid (CSF) obtained from MS patients on the secretory activity of WJ-MSCs and broaden this observation with WJ-MSCs interactions with human oligodendroglia cell line (OLs). Analysis of the WJ-MSCs secretory activity with use of Bio-Plex Pro™ Human Cytokine confirmed significant and diverse immunomodulatory potential. Our data reveal rich WJ-MSCs secretome with markedly increased levels of IL-6, IL-8, IP-10 and MCP-1 synthesis and a favourable profile of growth factors. The addition of MS CSF to the WJ-MSCs culture caused depletion of most proteins measured, only IL-12, RANTES and GM-CSF levels were increased. Most cytokines and chemokines decreased their concentrations in WJ-MSCs co-cultured with OLs, only eotaxin and RANTES levels were slightly increased. These results emphasize the spectrum of the immunomodulatory properties of WJ-MSCs and show how those effects can be modulated depending on the transplantation milieu.

Highlights

Multiple sclerosis (MS) is a neurological disorder with complex pathology, such as inflammation, demyelination, axonal loss, astrocytosis and microglia activation [1]
Secretome of WJ-mesenchymal stem cells (MSCs) Conditioned with MS and Control cerebrospinal fluid (CSF)
In the co-culture of Wharton’s jelly Mesenchymal Stem Cells (WJ-MSCs) and MO3.13 conducted with the addition of phorbol 12‐myristate acetate (PMA), we found the presence of Il-1b, interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 7 (IL-7), interleukin 8 (IL-8), eotaxin, IFN-γ, monocyte chemoattractant protein 1 (MCP-1), MIP-1α, RANTES, TNF-α and only one growth factor—fibroblast growth factor (FGF)

Summary

Introduction

Multiple sclerosis (MS) is a neurological disorder with complex pathology, such as inflammation, demyelination, axonal loss, astrocytosis and microglia activation [1]. Available therapies mostly use immunomodulatory drugs, which are effective, but especially so in the early stages of MS, when the inflammatory process in the central nervous system (CNS) is dominant. Cell-based therapy using transplantation of mesenchymal stem cells (MSCs) came as a novel approach to that issue, sparking interest and hope [3]. Initial data from experiments using MSCs treatment in animal models of MS—experimental autoimmune encephalomyelitis (EAE)—were promising, showing reduction of inflammatory infiltrates and demyelination areas, stimulating oligodendrogenesis, and increased brain derived neurotrophic factor (BDNF) expression [4,5,6,7]. The remyelination effect achieved in animal experiments was not extrapolated in humans by straight intracranial transplantation of oligodendrocyte progenitor cells (OPCs) or neural stem cells (NSCs) [8,9]. Transplantation of NSCs as a source of cytokines and neurotrophins for a local neuroprotective function, and an immunosuppressive response, is a promising therapeutic strategy [10,11]

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