Friday, 7 September 2012

Research: embryonic stem cells are immunosuppressive


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?

7 comments:

  1. Is it missing the rXr factor? (the gene(?) that the team in Cambridge think helps promote repair of myelin)

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  2. There was a report on the MSRC website today about a team in Cleveland who found that the important stuff to help the mice was not MSC's but the soup they were growing in- in particular hepatocyte growth factor. It's been/being reported in nature neurocscience. I'm probably putting it wrong, but it sounded very interesting

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  3. Dear Anon 5:26
    Yes I saw it too, if you go back to 23 May we reported on this very story

    http://multiple-sclerosis-research.blogspot.co.uk/2012/05/research-more-stem-cell-hype-or-it-it.html

    If you remember caused the the birth of a new term of the Blog the "Shania"

    It is watch this space along with RXR and the other recent X factors to promote remyelination reported recently. There is a question how to deliver this hepatocyte growth factor as it has been linked with promoting tumors, so as ever not plain sailing

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    Replies
    1. MouseDoctor, you seem to be very jaded when it comes to remyelination talk for progressive MSers. Why is that?

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  4. I am not jaded. This is about interpreting the Good, Bad and other News.

    If you want, every time I see someone saying that drug this or drug that is causing remyelination, neuroprotecting I will say that is great when the data does not or can not show what they are claiming. In the above case some work sounds interesting and some of it is misleading in my humble opinion

    We and EAE have been lambasted for not providing the treatments that we all want. This is because hype is created by the scientists over inflating the significance of their work and by people who appear to have insufficient concept of what it takes to get a drug licensed.

    If they did more compelling experiments I would be more compelled but so much of what I see is the same old, same old nonsense. Alot of the immune stuff is truly awful.

    I report on early remyelination studies here because that appears to interest you. I seldom report on experimental autoimmune studies. These are all science fiction and it takes years for things to become science fact.

    I guess I wouldn't make a good reporter because I am not upbeat about things and an not to keen on twisting the story. Sorry if you think you are getting the grumpy old man, but trying to keep it real.

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