Stem Cell Culture Media Improves EAE

Research Summary: Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Autoimmune Encephalomyelitis

The background

Current MS therapies mostly work to suppress the immune system, thus minimising the autoimmune damage on the central nervous system (CNS) seen in multiple sclerosis (MS).  However, these medications have little or no impact on reversing the disease process and repairing destroyed myelin.  For this reason, new treatments that are able to promote repair and remyelination are incredibly important.

The use of stem cells to provide targeted therapy for people with MS has become a topic of interest recently.  A type of stem cells, known as mesenchymal stem cells, have shown benefits and are currently being evaluated in clinical trials.  However, a number of studies have indicated that the improvements observed may not be entirely due to the stem cells replacing the damaged cells, but more from the signalling that these cells provide.

The study

Researchers from Nagoya University attempted to answer the question as to whether the signalling factor alone, without the cell graft, was enough to show therapeutic benefits.  For these experiments, mesenchymal stem cells were isolated and grown from the pulp found in baby teeth that had been removed for dental purposes.  After growing the cells, the culture medium (the liquid that the cells were incubated in) was separated from the cells and harvested.  This called medium was referred to as SHED-CM (stem cells from human exfoliated deciduous teeth culture medium).

Mice that had developed EAE were then injected with either SHED-CM or control culture medium that had not been incubated with the stem cells.  This injection was performed at the peak of EAE disease.

The findings

These experiments resulted in a number of findings, including:

• A single injection with SHED-CM decreased the severity in mice with EAE.  This reduction happened rapidly and was shown to be sustained across the course of the experiment.

• Analysis of tissue sections showed that mice treated with SHED-CM had less damage to their myelin and less infiltration of immune cells

• Treatment with SHED-CM had an anti-inflammatory effect, possibly due to converting a certain group of immune cells (known as macrophages) from one type to another – M1 to M2.  It is known that M2 macrophages can suppress inflammatory signals in the body, as well as clear myelin debris to promote remyelination.

• T cells known to be important in the progression of EAE were also cultured in SHED-CM and normal culture medium.  It was shown that in the presence of SHED-CM, these T cells did not become activated and proliferate, nor secrete pro-inflammatory molecules.

The outcomes

This study has shown that a single injection with SHED-CM has the ability to decrease the clinical severity of EAE in an animal model of MS.  In addition to this, it was shown that these benefits may occur through a variety of different functions that alter the immune response and allow for less damage and the potential for repair.

This suggests that SHED-CM, or particular molecules found in SHED-CM, may be useful and effective potential treatments for multiple sclerosis.  As these experiments have been performed in the animal model of MS, it will now be necessary to see whether similar results are seen in human trials.  As this therapeutic approach is “cell-free”, the authors suggest that it may be a safer alternative, however, long-term effects are still unknown.

The abstract for this article can be viewed here.