34. Stromal Vascular Fraction as a Novel Stem Cell-Based Therapy for a Mouse Model of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is the most common neurodegenerative disorder affecting young adults worldwide and remains an unmet clinical challenge. MS is caused by an autoimmune reaction against constituents of the central nervous system (CNS). Subsequent immune cell infiltration into CNS tissues lead to widespread inflammation, demyelination, and pathological lesions causing debilities such as tremors, fatigue, and progressive loss of motor functions. These pathological hallmarks are reproducible in the mouse experimental autoimmune encephalomyelitis (EAE) model of MS. Several clinical trials have demonstrated the safety and efficacy of adipose-derived stem cell (ASC)-based therapies in treating various disorders. ASC-based therapies are considered favorable due to their abundance in adult human adipose depots, less invasive harvest protocol, and potent immune-modulatory capabilities. However, due to the requisite for ex vivo culture isolation and expansion, alternative therapies are necessary. As such, the stromal vascular fraction (SVF) of adipose tissue has been considered a potential alternative to ASC-based therapies. The SVF consists of ASCs, adipocytes, and numerous leukocytes. The combination of cell types is believed to provide enhanced effectiveness by reducing inflammation and repairing damage. Currently, the SVF has advanced to clinical trials as a promising therapy for various medical indications including neurodegenerative diseases. Nevertheless, the efficacy of SVF therapy for MS patients or EAE mice has not been investigated. In this study, 1×106 SVF cells or ASCs were administered by intraperitoneal injected into EAE mice during the progression of disease, i.e. early, mid-stage, and chronic phases. Immune-modulatory activities of injected SVF and ASCs were analyzed using flow cytometry and qRT-PCR of lymphoid and CNS tissues and blood at the endpoint of the study. Both SVF and ASC treatments reduced pathological infiltrates and levels of inflammatory cytokines. Results show greater efficacy for reducing disease severity, recovery of motor functions, and improvement in histological examinations from EAE mice injected with SVF than ASCs, regardless of the timing. Together, SVF cells are more comprehensive at treating the immunopathogenesis of EAE by producing robust immune-modulatory effects. The translational aspects of this study support the use of SVF over ASCs as a prospective therapy for MS due to these promising results.