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Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery
Multiple sclerosis (MS) is an immune‐mediated disease of the central nervous system (CNS) with no effective treatment available for the chronic‐progressive stage. Cell therapy is a promising therapeutic approach for attenuating the immune‐mediated CNS process. Isolated and expanded human placental s...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442828/ https://www.ncbi.nlm.nih.gov/pubmed/28371563 http://dx.doi.org/10.5966/sctm.2015-0363 |
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author | Shapira, Ilona Fainstein, Nina Tsirlin, Maria Stav, Ilana Volinsky, Evgenia Moresi, Claudia Ben‐Hur, Tamir Gorodetsky, Raphael |
author_facet | Shapira, Ilona Fainstein, Nina Tsirlin, Maria Stav, Ilana Volinsky, Evgenia Moresi, Claudia Ben‐Hur, Tamir Gorodetsky, Raphael |
author_sort | Shapira, Ilona |
collection | PubMed |
description | Multiple sclerosis (MS) is an immune‐mediated disease of the central nervous system (CNS) with no effective treatment available for the chronic‐progressive stage. Cell therapy is a promising therapeutic approach for attenuating the immune‐mediated CNS process. Isolated and expanded human placental stromal cells (hPSCs) possess potent immunomodulatory and trophic properties, making them a good candidate for MS therapy. We examined the potential of hPSC therapy in preventing the onset or attenuating the course of established disease in a murine MS model of myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis. We examined the feasibility of hPSC systemic delivery by intramuscular (i.m.) implantation rather than the commonly used intravenous injection, which is dose‐limiting and carries the risk of pulmonary obstruction. Our findings showed significant attenuation of the disease only when hPSCs were injected directly to the central nervous system. Intramuscular implanted hPSCs survived at the site of injection for at least 2 months and elicited extensive local immune responses. Intramuscular hPSC implantation before disease onset caused a delay in the appearance of clinical signs and reduced the severity of a relapse induced by repeated challenge with the autoantigen. Intramuscular implantation after disease onset did not affect its course. Thus, pathological analysis of CNS tissue did not show inhibition of neuroinflammation in i.m. hPSC‐implanted mice. Moreover, no apparent effect was seen on the proliferative response of peripheral lymph node cells in these animals. We conclude that to maximize their therapeutic potential in MS, hPSCs should be delivered directly to the affected CNS. Stem Cells Translational Medicine 2017;6:1286–1294 |
format | Online Article Text |
id | pubmed-5442828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54428282017-06-15 Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery Shapira, Ilona Fainstein, Nina Tsirlin, Maria Stav, Ilana Volinsky, Evgenia Moresi, Claudia Ben‐Hur, Tamir Gorodetsky, Raphael Stem Cells Transl Med Translational Research Articles and Reviews Multiple sclerosis (MS) is an immune‐mediated disease of the central nervous system (CNS) with no effective treatment available for the chronic‐progressive stage. Cell therapy is a promising therapeutic approach for attenuating the immune‐mediated CNS process. Isolated and expanded human placental stromal cells (hPSCs) possess potent immunomodulatory and trophic properties, making them a good candidate for MS therapy. We examined the potential of hPSC therapy in preventing the onset or attenuating the course of established disease in a murine MS model of myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis. We examined the feasibility of hPSC systemic delivery by intramuscular (i.m.) implantation rather than the commonly used intravenous injection, which is dose‐limiting and carries the risk of pulmonary obstruction. Our findings showed significant attenuation of the disease only when hPSCs were injected directly to the central nervous system. Intramuscular implanted hPSCs survived at the site of injection for at least 2 months and elicited extensive local immune responses. Intramuscular hPSC implantation before disease onset caused a delay in the appearance of clinical signs and reduced the severity of a relapse induced by repeated challenge with the autoantigen. Intramuscular implantation after disease onset did not affect its course. Thus, pathological analysis of CNS tissue did not show inhibition of neuroinflammation in i.m. hPSC‐implanted mice. Moreover, no apparent effect was seen on the proliferative response of peripheral lymph node cells in these animals. We conclude that to maximize their therapeutic potential in MS, hPSCs should be delivered directly to the affected CNS. Stem Cells Translational Medicine 2017;6:1286–1294 John Wiley and Sons Inc. 2016-09-29 2017-04 /pmc/articles/PMC5442828/ /pubmed/28371563 http://dx.doi.org/10.5966/sctm.2015-0363 Text en © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Translational Research Articles and Reviews Shapira, Ilona Fainstein, Nina Tsirlin, Maria Stav, Ilana Volinsky, Evgenia Moresi, Claudia Ben‐Hur, Tamir Gorodetsky, Raphael Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery |
title | Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery |
title_full | Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery |
title_fullStr | Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery |
title_full_unstemmed | Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery |
title_short | Placental Stromal Cell Therapy for Experimental Autoimmune Encephalomyelitis: The Role of Route of Cell Delivery |
title_sort | placental stromal cell therapy for experimental autoimmune encephalomyelitis: the role of route of cell delivery |
topic | Translational Research Articles and Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442828/ https://www.ncbi.nlm.nih.gov/pubmed/28371563 http://dx.doi.org/10.5966/sctm.2015-0363 |
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