Research: embryonic stem cells are immunosuppressive

Epub: Kim et al. Immunomodulation by Transplanted Human Embryonic Stem Cell- Derived Oligodendroglial Progenitors in Experimental Autoimmune Encephalomyelitis. Stem Cells. 2012. doi: 10.1002/stem.1218.

Transplantation of embryonic stem cells and their neural derivatives can lead to amelioration of the disease symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Oligodendroglial progenitors (OPs), derived from human embryonic stem cells (hESC, HES-1), were labeled with superparamagnetic iron oxide and transduced with luciferase. At 7 days following induction of EAE in C57/BL6 mice, 1×10(6) cells were transplanted in the ventricles of C57/BL6 mice and non-invasively monitored by magnetic resonance and bioluminescence imaging. Cells were found to remain within the cerebroventricular system and did not survive for more than 10 days. However, EAE mice that received hESC-OPs showed a significant improvement in neurological disability scores (0.9±0.2; n=12) compared to that of control animals (3.3±0.4; n=12) at day 15 post-transplantation. Histopathologically, transplanted hESC-OPs generated TREM2-positive CD45 cells, increased TIMP-1 expression, confined inflammatory cells within the subarachnoid space, and gave rise to higher numbers of Foxp3-positive regulatory T cells in the spinal cord and spleen. Our results suggest that transplantation of hESC-OPs can alter the pathogenesis of EAE through immunomodulation, potentially providing new avenues for stem cell-based treatment of MS.



Human stem cells were used to generate immature oligodendrocytes and these were transplanted into the brain of mice with EAE after they had been made to contain some iron particles so that they could be tracked. After they were injected they stayed where they are and were dead within two weeks. The did not convert into to myelinating cells or nerves that the hype would leave us to believe. Were they rejected by the mouse,s immune system that would mean they would be quickly killed? ...well possibly. They generated macrophage-like cells, but they were probably there to clear up the dead transplanted cells. 

Their major benefit was that they appearred to modulate the immune response. These would therefore affect relapsing disease. This is why people involved in early trials with mesenchymal stem cells are being selected to be relapsing even if they have progressive MS.

We know that there are immature oligodendrocytes in the lesions of MS but they are not myelinating, so we need to change the environment  such that it is conducive to repair. Is it missing the X factor?

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