Some stem cells may not cause remeylination

Salinas Tejedor L, Berner G, Jacobsen K, Gudi V, Jungwirth N, Hansmann F, Gingele S, Prajeeth CK, Baumgärtner W, Hoffmann A, Skripuletz T, Stangel M. Mesenchymal stem cells do not exert direct beneficial effects on CNS remyelination in the absence of the peripheral immune system. Brain Behav Immun. 2015 Jun. pii: S0889-1591(15)00233-0

Remyelination is the natural repair mechanism in demyelinating disorders such as multiple sclerosis (MS) and it was proposed that it might protect from axonal loss. For unknown reasons, remyelination is often incomplete or fails in MS lesions and therapeutic treatments to enhance remyelination are not available. Recently, the transplantation of exogenous mesenchymal stem cells (MSC) has emerged as a promising tool to enhance repair processes. This included the animal model experimental autoimmune encephalomyelitis (EAE), a commonly used model for the autoimmune mechanisms of MS. However, in EAE it is not clear if the beneficial effect of MSC derives from a direct influence on brain resident cells or if this is an indirect phenomenon via modulation of the peripheral immune system. The aim of this study was to determine potential regenerative functions of MSC in the toxic cuprizone model of demyelination that allows studying direct effects on de- and remyelination without the influence of the peripheral immune system. MSC from three different species (human, murine, canine) were transplanted either intraventricularly into the cerebrospinal fluid or directly into the lesion of the corpus callosum at two time points: at the onset of oligodendrocyte progenitor cell (OPC) proliferation or the peak of OPC proliferation during cuprizone induced demyelination. Our results show that MSC did not exert any regenerative effects after cuprizone induced demyelination and oligodendrocyte loss. During remyelination, MSC did not influence the dynamics of OPC proliferation and myelin formation. In conclusion, MSC did not exert direct regenerative functions in a mouse model where peripheral immune cells and especially T lymphocytes do not play a role. We thus suggest that the peripheral immune system is required for MSC to exert their effects and this is independent from a direct influence of the central nervous system.

There are many types of stem cells, but the hope of MSers is that they will cause repair. In a recent debate on stem cells at the MS Society it was argued that (a) Stem cells have only a modest effect by causing immune modulation (b) Few cells can get into the CNS an (c) They don’t cause much remyelination. In this study they take one type of stem cell and they inject them into the brain of mice with mice with chemical-induce demyelination, which is used to study remyelination drugs and the stem cells do nothing towards repair.

In response to your desires these approaches have already been tried in MS…so are they going to work? Maybe an Maybe not. However, the expectation should not be too unrealistically high.
If they do, things can be better an if they don’t…do not blame the animals.

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  • Has the STREAMS trial that uses mesenchymal stem cells got beyond 'it seems safe' to producing any results re its efficacy?

    • Maybe none, is it too late to affect the funding of the study…however could it affect recruitment.

      I have a post entitled Will ignoring the voice of class mates lead to bad test results…should I post it.

      It has nothing to do with stem cells or sodium channel blockers, buy here is a scenario.

      I think that sodium channels will be useful in slowing progression and so plan to do a trial but someone says they don't work and what's more it causes side-effects would you go on the study?

      So we have the sodium channel blocker called oxcarbazepine which we want to study in the PROXIMUS trial. However someone (neuro) says Lamotrigine, another sodium trail blocker did not work in progressive MS and whats more it caused side effects. Will you go on the oxcarbazepine trial?

      More people need to otherwise it will fail. Now I could argue that the neuro needs to pull their heads out from the dark place because phenytonin, another sodium channel bloggers saved nerves and the lamotrigine trial failed for the obvious fact that people were not taking their meds and so the oxcarbazepine trial has been unduly delayed for no good reason.

      To post or not to post that is the reason..

    • So once again, look for all the information before making a judgement, and be aware that some of the information you need might not exist yet.

      Two people try to cross a lake in kayaks. Just because the first person fails to make it across, it doesn't mean the second one will also fail … or something like that. Everyone should still sign up to kayak across the lake!

  • This may be a bit from left field, but as the subject is stem cells, I thought I'd bring it up. This trial for stem cell use in heart failure appears to show that the actual scars on the patients' hearts are actually healing with the treatment:

    They're claiming a 40% reduction in scar size.

    Would it be utter lunacy to think that if stem cells can reduce a scar in heart tissue, that they might also be effective in shrinking scarring on a spinal cord, or in a patient's brain? Perhaps if they were delivered directly to the patient's CNS in some manner?

    The trial also shows an improvement in ventricular ejection fraction. At the very least, maybe Fingolimod users who've had permanent heart effects can sign up for this treatment in a few years, and get their tickers tip top again, eh? It's somewhat uplifting stuff – even if there is a million logical reasons why it wouldn't work in MS.

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