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Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis

INTRODUCTION: While administration of ex vivo culture-expanded stem cells has been used to study immunosuppressive mechanisms in multiple models of autoimmune diseases, less is known about the uncultured, nonexpanded stromal vascular fraction (SVF)-based therapy. The SVF is composed of a heterogeneo...

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Autores principales: Semon, Julie A, Maness, Catherine, Zhang, Xiujuan, Sharkey, Steven A, Beuttler, Marc M, Shah, Forum S, Pandey, Amitabh C, Gimble, Jeffrey M, Zhang, Shijia, Scruggs, Brittni A, Strong, Amy L, Strong, Thomas A, Bunnell, Bruce A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054950/
https://www.ncbi.nlm.nih.gov/pubmed/24405805
http://dx.doi.org/10.1186/scrt391
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author Semon, Julie A
Maness, Catherine
Zhang, Xiujuan
Sharkey, Steven A
Beuttler, Marc M
Shah, Forum S
Pandey, Amitabh C
Gimble, Jeffrey M
Zhang, Shijia
Scruggs, Brittni A
Strong, Amy L
Strong, Thomas A
Bunnell, Bruce A
author_facet Semon, Julie A
Maness, Catherine
Zhang, Xiujuan
Sharkey, Steven A
Beuttler, Marc M
Shah, Forum S
Pandey, Amitabh C
Gimble, Jeffrey M
Zhang, Shijia
Scruggs, Brittni A
Strong, Amy L
Strong, Thomas A
Bunnell, Bruce A
author_sort Semon, Julie A
collection PubMed
description INTRODUCTION: While administration of ex vivo culture-expanded stem cells has been used to study immunosuppressive mechanisms in multiple models of autoimmune diseases, less is known about the uncultured, nonexpanded stromal vascular fraction (SVF)-based therapy. The SVF is composed of a heterogeneous population of cells and has been used clinically to treat acute and chronic diseases, alleviating symptoms in a range of tissues and organs. METHODS: In this study, the ability of human SVF cells was compared with culture-expanded adipose stem cells (ASCs) and bone-derived marrow stromal cells (BMSCs) as a treatment of myelin oligodendrocyte glycoprotein (35–55)-induced experimental autoimmune encephalitis in C57Bl/6J mice, a well-studied multiple sclerosis model (MS). A total of 1 × 10(6) BMSCs, ASCs, or SVF cells were administered intraperitoneally concomitantly with the induction of disease. Mice were monitored daily for clinical signs of disease by three independent, blinded investigators and rated on a scale of 0 to 5. Spinal cords were obtained after euthanasia at day 30 and processed for histological staining using luxol fast blue, toluidine blue, and hematoxylin and eosin to measure myelin and infiltrating immune cells. Blood was collected from mice at day 30 and analyzed by enzyme-linked immunosorbent assay to measure serum levels of inflammatory cytokines. RESULTS: The data indicate that intraperitoneal administration of all cell types significantly ameliorates the severity of disease. Furthermore, the data also demonstrate, for the first time, that the SVF was as effective as the more commonly cultured BMSCs and ASCs in an MS model. All cell therapies also demonstrated a similar reduction in tissue damage, inflammatory infiltrates, and sera levels of IFNγ and IL-12. While IFNγ levels were reduced to comparable levels between treatment groups, levels of IL-12 were significantly lower in SVF-treated than BMSC-treated or ASC-treated mice. CONCLUSIONS: Based on these data, it is evident that SVF cells have relevant therapeutic potential in an animal model of chronic MS and might represent a valuable tool for stem cell-based therapy in chronic inflammatory disease of the central nervous system. SVF offers advantages of direct and rapid isolation procedure in a xenobiotic-free environment.
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spelling pubmed-40549502014-06-15 Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis Semon, Julie A Maness, Catherine Zhang, Xiujuan Sharkey, Steven A Beuttler, Marc M Shah, Forum S Pandey, Amitabh C Gimble, Jeffrey M Zhang, Shijia Scruggs, Brittni A Strong, Amy L Strong, Thomas A Bunnell, Bruce A Stem Cell Res Ther Research INTRODUCTION: While administration of ex vivo culture-expanded stem cells has been used to study immunosuppressive mechanisms in multiple models of autoimmune diseases, less is known about the uncultured, nonexpanded stromal vascular fraction (SVF)-based therapy. The SVF is composed of a heterogeneous population of cells and has been used clinically to treat acute and chronic diseases, alleviating symptoms in a range of tissues and organs. METHODS: In this study, the ability of human SVF cells was compared with culture-expanded adipose stem cells (ASCs) and bone-derived marrow stromal cells (BMSCs) as a treatment of myelin oligodendrocyte glycoprotein (35–55)-induced experimental autoimmune encephalitis in C57Bl/6J mice, a well-studied multiple sclerosis model (MS). A total of 1 × 10(6) BMSCs, ASCs, or SVF cells were administered intraperitoneally concomitantly with the induction of disease. Mice were monitored daily for clinical signs of disease by three independent, blinded investigators and rated on a scale of 0 to 5. Spinal cords were obtained after euthanasia at day 30 and processed for histological staining using luxol fast blue, toluidine blue, and hematoxylin and eosin to measure myelin and infiltrating immune cells. Blood was collected from mice at day 30 and analyzed by enzyme-linked immunosorbent assay to measure serum levels of inflammatory cytokines. RESULTS: The data indicate that intraperitoneal administration of all cell types significantly ameliorates the severity of disease. Furthermore, the data also demonstrate, for the first time, that the SVF was as effective as the more commonly cultured BMSCs and ASCs in an MS model. All cell therapies also demonstrated a similar reduction in tissue damage, inflammatory infiltrates, and sera levels of IFNγ and IL-12. While IFNγ levels were reduced to comparable levels between treatment groups, levels of IL-12 were significantly lower in SVF-treated than BMSC-treated or ASC-treated mice. CONCLUSIONS: Based on these data, it is evident that SVF cells have relevant therapeutic potential in an animal model of chronic MS and might represent a valuable tool for stem cell-based therapy in chronic inflammatory disease of the central nervous system. SVF offers advantages of direct and rapid isolation procedure in a xenobiotic-free environment. BioMed Central 2014-01-09 /pmc/articles/PMC4054950/ /pubmed/24405805 http://dx.doi.org/10.1186/scrt391 Text en Copyright © 2014 Semon et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Semon, Julie A
Maness, Catherine
Zhang, Xiujuan
Sharkey, Steven A
Beuttler, Marc M
Shah, Forum S
Pandey, Amitabh C
Gimble, Jeffrey M
Zhang, Shijia
Scruggs, Brittni A
Strong, Amy L
Strong, Thomas A
Bunnell, Bruce A
Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
title Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
title_full Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
title_fullStr Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
title_full_unstemmed Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
title_short Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
title_sort comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4054950/
https://www.ncbi.nlm.nih.gov/pubmed/24405805
http://dx.doi.org/10.1186/scrt391
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