Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis
BioMed Central Ltd.
Stem Cell Research & Therapy 2014, 5:2 doi:10.1186/scrt391
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
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.
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 1×106 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.
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 IFNγand 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.
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.
There is an increasing interest in the biology and therapeutic potential of the SVF due to the direct and rapid isolation procedure in a xenobiotic-reduced environment [41,42,51]. Whether the potency of the SVF is a result of the fact that the cells do not undergo extensive ex vivo culture because the injected cells are a mix of ASCs in combination with lymphohematopoietic and other cell types or a combination of both needs to be further determined. Regardless, the findings demonstrate that when compared with ex vivoexpanded ASCs, SVF cells are equivalent to cultured cells in their ability to ameliorate EAE disease progression, and further reduce Th1-type cytokines. Moreover, the SVF is simple and straightforward to isolate. The 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 CNS.