Immunomodulatory Effects of Adipose Stromal Vascular Fraction Cells Promote Alternative Activation Macrophages to Repair Tissue Damage

• Published in: Stem cells (Dayton, Ohio) Vol. 35; no. 10; pp. 2198 - 2207
• Main Authors: Bowles, Annie C., Wise, Rachel M., Gerstein, Brittany Y., Thomas, Robert C., Ogelman, Roberto, Febbo, Isabella, Bunnell, Bruce A.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.10.2017
• Subjects: Adipocytes - metabolism; Adipocytes - pathology; Adipose stem cells; Adipose Tissue - metabolism; Alternative activation macrophages; Animal tissues; Animals; Cell activation; Central nervous system; Demyelination; Dichotomies; Disease Models, Animal; Experimental allergic encephalomyelitis; Helper cells; Immunology; Immunomodulation; Immunomodulation - immunology; Immunoregulation; Inflammation; Interleukin 10; Lesions; Localization; Lymphocytes; Lymphocytes T; Lymphoid tissue; Macrophages; Macrophages - metabolism; Mice; Multiple sclerosis; Neurodegeneration; Pathogenesis; Regeneration; Repair; Rodents; Stem cell therapy; Stem cell transplantation; Stem cells; Stromal cells; Stromal Cells - metabolism; Stromal Cells - pathology; Th1/Th2; Th1/Th2; Adipose stem cells; Immunomodulation; Neurodegeneration; Stromal cells; Alternative activation macrophages; Stem cell therapy
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.2689

The pathogenesis of many diseases is driven by the interactions between helper T (TH) cells and macrophages. The phenotypes of these cells are functional dichotomies that are persuaded according to the surrounding milieu. In both multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, TH1 and TH17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this proinflammatory repertoire promotes the classical activation, formerly the M1‐type, macrophages. Together, these cells infiltrate into the central nervous system (CNS) tissues and generate inflammatory and demyelinating lesions. Our most recent report demonstrated the immunomodulatory and anti‐inflammatory effects of adipose stromal vascular fraction (SVF) cells and adipose‐derived stem cells (ASCs) that led to functional, immunological, and pathological improvements in the EAE model. Here, a deeper investigation revealed the induction of regulatory T cells and alternative activation, or M2‐type, macrophages in the periphery followed by the presence of alternative activation macrophages, reduced cellular infiltrates, and attenuation of neuroinflammation in CNS tissues following intraperitoneal administration of these treatments. Spleens from treated EAE mice revealed diminished TH1 and TH17 cell activities and were markedly higher in the levels of anti‐inflammatory cytokine interleukin‐10. Interestingly, SVF cells were more effective than ASCs at mediating these beneficial changes, which were attributed to their localization to the spleens after administration. Together, SVF cells rapidly and robustly attenuated the propagation of autoimmune signaling in the periphery that provided a permissive milieu in the CNS for repair and possibly regeneration. Stem Cells 2017;35:2198–2207 Schematic collectively showing results that lead to improvements in encephalomyelitis (EAE) mice following treatment with stromal vascular fraction (SVF) cells and adipose‐derived stem cells (ASCs).