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Stem Cells. 2017 Oct;35(10):2198-2207. doi: 10.1002/stem.2689. Epub 2017 Aug 21.

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

Author information

1
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
2
Department of Cell and Molecular Biology, Tulane University School of Science and Engineering, New Orleans, Louisiana, USA.
3
Neuroscience Program, Tulane University School of Science and Engineering, New Orleans, Louisiana, USA.
4
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA.

Abstract

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, TH 1 and TH 17 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 TH 1 and TH 17 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.

KEYWORDS:

Adipose stem cells; Alternative activation macrophages; Immunomodulation; Neurodegeneration; Stem cell therapy; Stromal cells; Th1/Th2

PMID:
28801931
DOI:
10.1002/stem.2689
[Indexed for MEDLINE]
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