Stem cells promoting repair

Glenn JD, Smith MD, Kirby LA, Baxi EG, Whartenby KA. Disparate Effects of Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis and Cuprizone-Induced Demyelination. PLoS One. 2015 Sep 25;10(9):e0139008.

Mesenchymal stem cells (MSCs) are pleiotropic cells with potential therapeutic benefits for a wide range of diseases. Because of their immunomodulatory properties they have been utilized to treat autoimmune diseases such as multiple sclerosis (MS), which is characterized by demyelination. The microenvironment surrounding MSCs is thought to affect their differentiation and phenotype, which could in turn affect the efficacy. We thus sought to dissect the potential for differential impact of MSCs on central nervous system (CNS) disease in T cell mediated and non-T cell mediated settings using the MOG35-55 experimental autoimmune encephalomyelitis (EAE) and cuprizone-mediated demyelination models, respectively. As the pathogeneses of MS and EAE are thought to be mediated by IFNγ-producing (TH1) and IL-17A-producing (TH17) effector CD4+ T cells, we investigated the effect of MSCs on the development of these two key pathogenic cell groups. Although MSCs suppressed the activation and effector function of TH17 cells, they did not affect TH1 activation, but enhanced TH1 effector function and ultimately produced no effect on EAE. In the non- T cell mediated cuprizone model of demyelination, MSC administration had a positive effect, with an overall increase in myelin abundance in the brain of MSC-treated mice compared to controls. These results highlight the potential variability of MSCs as a biologic therapeutic tool in the treatment of autoimmune disease and the need for further investigation into the multifaceted functions of MSCs in diverse microenvironments and the mechanisms behind the diversity.

So you wanted stem cells and you are getting trials in stem cells, but should we be running before we can walk. The answer is its too late the studies are happening . But this study underscores the problem. The results were hyped and were either marginally effective or as shown here they were ineffective and so now we wait for the results in MS. Lets hope they are fantastic but I fear not. This study argues that mesenchymal stem cells are pretty rubbish in EAE and so pretty rubbish as an immune modulator.
I have argued numerous times however that current DMT can do more than these stem cells. 

What we want to see is repair because this is why you want stem cell studies. In this study there is a suggestion that the stem cells can promote repair here, but in other studies this effect has been weak.

What will the human trials show?

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  • It would be interesting to see a study of MSCs following a lymphocyte ablation therapy such as Alemtuzumab which has been shown to deplete Th1 and Th17 populations.

    • It has already been done I think, many studies have been done using Alemtuzumab….and the results are about as good as using alemtuzumab

  • Doesn't the most commonly used HTSC protocol use Alemtuzumab as the depletion chemical? Ergo, the benefits of the stem cells may never have been anything more than a lifted neuroprotective ceiling…

    • If you are doing HSCT then you can be brutal in removing the lymphoid system and give alemtuzuamab cyclophosphamide etc etc this depletion regime may be the key to success and have nothing to do with the HSC, but they are vital to protect you from infection

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