title: Adipose Stromal Vascular Fraction-Mediated Improvements at Late-Stage Disease in a Murine Model of Multiple Sclerosis.
abstract: Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes. The SVF can be culture expanded to generate ASC lines. Clinical trials continue to demonstrate the safety and efficacy of ASC therapies for treating several diseases. However, little is known about the effectiveness of the SVF for neurodegenerative diseases, such as MS. At late-stage disease, EAE mice show severe motor impairment. The goal for these studies was to test the effectiveness of SVF cells and ASC in EAE mice after the onset of neuropathology. The clinical scoring, behavior, motor function, and histopathologic analyses revealed significant improvements in EAE mice treated with the SVF or ASC. Moreover, SVF treatment mediated more robust improvements to CNS pathology than ASC treatment based on significant modulations of inflammatory factors. The most pronounced changes following SVF treatment were the high levels of interleukin-10 in the peripheral blood, lymphoid and CNS tissues along with the induction of regulatory T cells in the lymph nodes which indicate potent immunomodulatory effects. The data indicate SVF cells effectively ameliorated the EAE immunopathogenesis and supports the potential use of SVF for treating MS. Stem Cells 2017;35:532-544.
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.|Department of Cell and Molecular Biology, Tulane University School of Science and Engineering, New Orleans, Louisiana, USA.
authors.forename: Annie C
authors.initials: AC
authors.lastname: Bowles
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Strong
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.|Neuroscience Program, Tulane University School of Science and Engineering, New Orleans, Louisiana, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Wise
authors.affiliation: Neuroscience Program, Tulane University School of Science and Engineering, New Orleans, Louisiana, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Thomas
authors.affiliation: Neuroscience Program, Tulane University School of Science and Engineering, New Orleans, Louisiana, USA.
authors.forename: Brittany Y
authors.initials: BY
authors.lastname: Gerstein
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Dutreil
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Hunter
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.|Department of Medicine, Structural and Cellular Biology, and Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA.|LaCell LLC, New Orleans, Louisiana, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.|Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009103:Multiple Sclerosis / Q000097:blood / Q000473:pathology* / Q000628:therapy*; D010641:Phenotype; D013116:Spinal Cord / Q000473:pathology; D017154:Stromal Cells / Q000166:cytology
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D018836:Inflammation Mediators
keywords: Adipose; Experimental autoimmune encephalomyelitis; Immunomodulation; Multiple sclerosis; Stromal vascular fraction