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 heterogeneou...
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Online Access: | Semon et al. Stem Cell Research & Therapy 2014, 5:2 http://stemcellres.com/content/5/1/2 http://hdl.handle.net/10150/610253 http://arizona.openrepository.com/arizona/handle/10150/610253 |
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ndltd-arizona.edu-oai-arizona.openrepository.com-10150-6102532016-05-22T03:01:56Z Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis Semon, Julie Maness, Catherine Zhang, Xiujuan Sharkey, Steven Beuttler, Marc Shah, Forum Pandey, Amitabh Gimble, Jeffrey Zhang, Shijia Scruggs, Brittni Strong, Amy Strong, Thomas Bunnell, Bruce Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, 1430 Tulane Avenue, SL-99, New Orleans, LA 70112, USA Department of Cell and Molecular Biology, School of Science and Engineering, Tulane University, 6400 Freret Street, New Orleans, LA 70118, USA Department of Pharmacology, School of Medicine, Tulane University, 1430 Tulane Avenue, SL-83, New Orleans, LA 70112, USA Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA 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 1x106 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 IFNgamma and IL-12. While IFNgamma 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. 2014 Article Semon et al. Stem Cell Research & Therapy 2014, 5:2 http://stemcellres.com/content/5/1/2 10.1186/scrt391 http://hdl.handle.net/10150/610253 http://arizona.openrepository.com/arizona/handle/10150/610253 1757-6512 Stem Cell Research & Therapy en http://stemcellres.com/content/5/1/2 © 2014 Semon et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0) BioMed Central |
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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 1x106 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 IFNgamma and IL-12. While IFNgamma 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. |
author2 |
Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, 1430 Tulane Avenue, SL-99, New Orleans, LA 70112, USA |
author_facet |
Center for Stem Cell Research and Regenerative Medicine, School of Medicine, Tulane University, 1430 Tulane Avenue, SL-99, New Orleans, LA 70112, USA Semon, Julie Maness, Catherine Zhang, Xiujuan Sharkey, Steven Beuttler, Marc Shah, Forum Pandey, Amitabh Gimble, Jeffrey Zhang, Shijia Scruggs, Brittni Strong, Amy Strong, Thomas Bunnell, Bruce |
author |
Semon, Julie Maness, Catherine Zhang, Xiujuan Sharkey, Steven Beuttler, Marc Shah, Forum Pandey, Amitabh Gimble, Jeffrey Zhang, Shijia Scruggs, Brittni Strong, Amy Strong, Thomas Bunnell, Bruce |
spellingShingle |
Semon, Julie Maness, Catherine Zhang, Xiujuan Sharkey, Steven Beuttler, Marc Shah, Forum Pandey, Amitabh Gimble, Jeffrey Zhang, Shijia Scruggs, Brittni Strong, Amy Strong, Thomas Bunnell, Bruce Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis |
author_sort |
Semon, Julie |
title |
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_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_sort |
comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis |
publisher |
BioMed Central |
publishDate |
2014 |
url |
Semon et al. Stem Cell Research & Therapy 2014, 5:2 http://stemcellres.com/content/5/1/2 http://hdl.handle.net/10150/610253 http://arizona.openrepository.com/arizona/handle/10150/610253 |
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