[Sciences] Interim report on using mesenchymal stem cells in multiple sclerosis: is a stem-cell therapy within reach?

Multiple sclerosis is a autoimmune disease that fascinates me. The reason it fascinates it is because it affects the central central nervous system and until now (like other neurological diseases) there is no FDA-approved drug for it. Patients undergo a progressive series of seizures followed by relapse and remission, each time things getting worse and loose motor function (10 years span between the time they are diagnosed and their death). Its origin is unknown but what we know is the blood-brain barrier (BBB) plays a key role in the disease. Under normal condition, the central nervous system is qualified as “neuroimmune privileged tissue”. In other words, it means that the central nervous system is devoid of the normal immune cells we know and fight infections.
We know that some lymphocytes, the Th17, are activated against some proteins present in the brain, among them the myelin basic protein (MBP). MBP is expressed by oligodendrocytes that look like “octopus cells” wrapping their tentacles full of myelin (a type of fatty acid) around axons. By analogy, these axons are like electric copper wires and as in real-life copper wires have to be insulated to conduct electricity. Myelin sheets play the same role.
So we have these Th17 that normally should have been eliminated (as they are autoimmune and therefore dangerous) but they are still circulating in the bloodstream. For some reasons, the BBB undergo an “activation”, that results in the exposure of little anchors on the blood side. These anchors can hook on the Th17, allowing them to undergo a series of complex moves on the BBB surface to finally cross over it and reach the CNS. At this point the Th17 detect endogenous proteins as foreign agents, instructs the killing of the oligodendrocytes and further induce damage by disrupting the BBB, make it leaky and allow the infiltration of other immune cells (including macrophage).

Recently a interim report published in JAMA by Bowen and colleagues (http://www.ncbi.nlm.nih.gov/pubmed/25546364) have used autologous stem cell transplant, using blood stem cells (referred as CD34+ cells, that in my mind would put them in the same group than endothelial progenitor cells). Interestingly so far (I have not read yet the full paper), the median survival at 3 years was oscillating between 86% (relapse-free) and 90% (progression-free) compared to 78% (placebo). That is a very interesting and promising news and nicely matches with a animal study by Pachter and colleagues (http://www.ncbi.nlm.nih.gov/pubmed/25068126) that used human embryonic stem cells derived into mesenchymal stem cells (hESC-MSCs so you can make a call that these cells are more undifferentiated than the CD34+ cells). The authors also found an improved clinical score in mice treated with hESC-MSCs compared to untreated cells but more importantly the hESC-MSCs have a better outcome than adult MSCs (obtained from bone marrow). Now the question is what happen to these cells? And more importantly how are the pericytes playing a role in this game? Parasites are certainly the “black box” cells of the BBB. We don’t exactly where they come from but some indications tells me that parasites and MSCs have something in common and I would not be surprised in the next decade, our dogma on pericytes switch them as standby mesenchymal stem cells around the BBB, waiting for an injury to occur to rescue and heal the damage area.

So yes, I am really looking forward to see how stem cell therapies will progress in neurological diseases because there could be some exciting new avenues in my research 🙂

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