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Stem Cells Straight from the Source Prove Therapeutically Relevant for MS



Adult stem cell therapies usually rely on extraction, purification, expansion and then re-infusion/re-implantation, with each stage entailing their own specific risks and disadvantages. Adipose-derived stem cells (ASCs) are a therapeutically important cell type taken from the stromal vascular fraction (SVF) made up of numerous cell types: vascular smooth muscle cells, fibroblasts, mast cells, macrophages, lymphocytes, endothelial cells, preadipocytes, as well as ASCs (see paper for extensive references). Both ASCs and SVF cells have been used to treat a range of diseases (Tran and Kahn, and Weisberg et al) and herein Semin et al describe their work comparing ASCs and SVF cells in an experimental model of Multiple sclerosis (MS) (Racke) - an autoimmune disease characterized mainly by inflammatory demyelinating lesions and loss of motor function. The researchers, from the laboratory of Bruce A. Bunnell at the Tulane University School of Medicine, New Orleans, Louisiana, USA, now report in Stem Cells Translational Medicine that while both ASCs and SVF cells effectively inhibited disease severity with a reduction in tissue damage, inflammation, SVF cells proved to be statistically more effective.

Semin et al first extracted SVF cells with a viability of 89%-94% from the adipose tissue of 2–6-month old male mice. These cells included committed adipocyte progenitors (26.26%) and ASCs (21.38%) with an additional 24.31% leukocyte cells, 7.98% hematopoietic stem cell-like cells, and 4.20% T-cells. ASCs from this fraction were CD29+Sca-1+CD106+ and CD31-CD11b-CD45- and were able to undergo adipogenic and osteogenic lineage differentiation. Using myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (EAE) in C57Bl/6J mice as a model system for MS, the authors demonstrated that intraperitoneal injection of only SVF cells halted disease progression when compared with controls treated with a vehicle alone. Normal disease development exhibits first clinical signs at 9 days and hind limb paralysis at 14 days; however ASCs delayed clinical signs only slightly (9.3 days), whereas SVF cell treated mice displayed disease onset at 14 days. Excitingly, only 3 of the 12 mice treated with SVF cells showed any clinical signs at all, indicating that SVF cells have a very potent neuroprotective effect. Analysis of pathological features through examination of spinal cord found reduced demyelination and reduced levels of myelin breakdown products and debris in both ASC and SVF treated mice. Furthermore infiltrating cells were significantly decreased compared to control. Finally sera levels of interleukin-12 (IL-12), and interferon-γ (IFN-γ), cytokines that play a central role in the pathology of MS (Chen et al and Reynolds et al) were analysed and found to be reduced similarly in both ASC and SVF cell injection although Tumor necrosis factor-α (TNFα) levels were unchanged.

While the authors do note that more work is still required to better understand the exact mechanisms behind the enhanced therapeutic function of total SVF cell over ASCs, they have demonstrated that SVF cells have many advantages over ASCs: they do not require ex vivo expansion, they are easy to attain, and they reduce disease progression and pathology, and so may represent a valuable therapeutic tool for MS treatment and potentially other diseases/disorders.

Chen SJ et al. (2012)
Current status of the immunomodulation and immunomediated therapeutic strategies for multiple sclerosis.
Clin Dev Immunol 2012:970789

Racke MK (2001)
Experimental autoimmune encephalomyelitis (EAE) Curr Protoc Neurosci, Chapter 9:Unit 9.7

Reynolds JM et al. (2012)
Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation.
Proc Natl Acad Sci USA 109:13064–13069

Tran TT, Kahn CR (2010)
Transplantation of adipose tissue and stem cells: Role in metabolism and disease.
Nat Rev Endocrinol 6:195–213

Weisberg SP et al. (2003)
Obesity is associated with macrophage accumulation in adipose tissue.
J Clin Invest 112:1796–1808

Stem Cells Correspondent Stuart P Atkinson reports on those studies appearing in current journals that are destined to make an impact on stem cell research and clinical studies.