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Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination
INTRODUCTION: White matter diseases are often accompanied by microglial activation and neuroinflammation. Mesenchymal stromal cells (MSCs) manufactured from umbilical cord tissue possess immunomodulatory properties, making them promising candidates for cell therapy in white matter disease. MSCs can...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476944/ http://dx.doi.org/10.1093/stcltm/szad047.030 |
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author | Xu, Li Min, Hyunjung Parrott, Roberta Kurtzberg, Joanne Filiano, Anthony |
author_facet | Xu, Li Min, Hyunjung Parrott, Roberta Kurtzberg, Joanne Filiano, Anthony |
author_sort | Xu, Li |
collection | PubMed |
description | INTRODUCTION: White matter diseases are often accompanied by microglial activation and neuroinflammation. Mesenchymal stromal cells (MSCs) manufactured from umbilical cord tissue possess immunomodulatory properties, making them promising candidates for cell therapy in white matter disease. MSCs can interact with resident macrophages and modify the course of inflammation. However, the influence MSCs have on microglia, the resident macrophages of the central nervous system (CNS), and its implications for white matter disease remain uncertain. OBJECTIVES: From the blood, MSCs traffic to lung and interact with resident macrophages to alter the trajectory of inflammation. We hypothesized that MSCs injected into the cerebrospinal fluid (CSF) would similarly suppress the activation of microglia. Our goals in this study were to test the efficacy MSCs have on microglia activation and develop a relevant potency assay. METHODS: In this study, we employed a range of assays, including an in vivo acute spinal cord demyelination model, organotypic brain slice cultures, and microglia activation assays with primary microglia and an immortalized cell line. Using these assays, we assessed the impact cord tissue derived MSCs have on microglial activation. RESULTS: In spinal cords and brain slices, lysophosphatidylcholine produced robust demyelination and microglia activation that was suppressed by MSCs. To determine if MSCs could directly impact microglia, we isolated primary microglia and activated them in culture with lipopolysachride (LPS), a toll-like receptor agonist. We screen 6 cytokines induced by LPS and determined that MSCs suppress the release of tumor necrosis factor (TNF) from LPS-activated microglia. We confirmed these results in vivo as MSCs blocked TNF production by spinal cord microglia after acute demyelination in the spinal cord. Additionally, we confirmed the ability of MSCs to suppress TNF in a simple assay with a microglia cell line (IMG). DISCUSSION: In this study, we demonstrated that cord tissue MSCs altered the immune response, suppressed microglia activation, and the release of TNF, a cytokine known to contribute to white matter damage. Among these assays, IMG could be standardized as an effective potency assay to determine the efficacy of MSC for the use in treatment of white matter disease. |
format | Online Article Text |
id | pubmed-10476944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-104769442023-09-05 Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination Xu, Li Min, Hyunjung Parrott, Roberta Kurtzberg, Joanne Filiano, Anthony Stem Cells Transl Med Preclinical Studies INTRODUCTION: White matter diseases are often accompanied by microglial activation and neuroinflammation. Mesenchymal stromal cells (MSCs) manufactured from umbilical cord tissue possess immunomodulatory properties, making them promising candidates for cell therapy in white matter disease. MSCs can interact with resident macrophages and modify the course of inflammation. However, the influence MSCs have on microglia, the resident macrophages of the central nervous system (CNS), and its implications for white matter disease remain uncertain. OBJECTIVES: From the blood, MSCs traffic to lung and interact with resident macrophages to alter the trajectory of inflammation. We hypothesized that MSCs injected into the cerebrospinal fluid (CSF) would similarly suppress the activation of microglia. Our goals in this study were to test the efficacy MSCs have on microglia activation and develop a relevant potency assay. METHODS: In this study, we employed a range of assays, including an in vivo acute spinal cord demyelination model, organotypic brain slice cultures, and microglia activation assays with primary microglia and an immortalized cell line. Using these assays, we assessed the impact cord tissue derived MSCs have on microglial activation. RESULTS: In spinal cords and brain slices, lysophosphatidylcholine produced robust demyelination and microglia activation that was suppressed by MSCs. To determine if MSCs could directly impact microglia, we isolated primary microglia and activated them in culture with lipopolysachride (LPS), a toll-like receptor agonist. We screen 6 cytokines induced by LPS and determined that MSCs suppress the release of tumor necrosis factor (TNF) from LPS-activated microglia. We confirmed these results in vivo as MSCs blocked TNF production by spinal cord microglia after acute demyelination in the spinal cord. Additionally, we confirmed the ability of MSCs to suppress TNF in a simple assay with a microglia cell line (IMG). DISCUSSION: In this study, we demonstrated that cord tissue MSCs altered the immune response, suppressed microglia activation, and the release of TNF, a cytokine known to contribute to white matter damage. Among these assays, IMG could be standardized as an effective potency assay to determine the efficacy of MSC for the use in treatment of white matter disease. Oxford University Press 2023-09-04 /pmc/articles/PMC10476944/ http://dx.doi.org/10.1093/stcltm/szad047.030 Text en © The Author(s) 2023. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Preclinical Studies Xu, Li Min, Hyunjung Parrott, Roberta Kurtzberg, Joanne Filiano, Anthony Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination |
title | Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination |
title_full | Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination |
title_fullStr | Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination |
title_full_unstemmed | Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination |
title_short | Abstract 29 Umbilical Cord-derived Mesenchymal Stromal Cells Suppress Microglia Activation Induced by Demyelination |
title_sort | abstract 29 umbilical cord-derived mesenchymal stromal cells suppress microglia activation induced by demyelination |
topic | Preclinical Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10476944/ http://dx.doi.org/10.1093/stcltm/szad047.030 |
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