Saturday, 29 September 2012

Neural Stem Cells Will be No Use as Immunomodulators


Foetal neural stem/precursor cells (NPCs) possess powerful immunomodulatory properties which enable them to protect the brain from immune-mediated injury. A major issue in developing neural stem/precursor cell (NPC) therapy for chronic neuroinflammatory disorders such as multiple sclerosis is whether cells maintain their immune-regulatory properties for prolonged periods of time. Therefore, we studied time-associated changes in NPC immunomodulatory properties. We examined whether intracerebrally-transplanted NPCs are able to inhibit early versus delayed induction of autoimmune brain inflammation and whether allogeneic NPC grafts continuously inhibit host rejection responses. In two experimental designs, intraventricular foetal NPC grafts attenuated clinically and pathologically brain inflammation during early EAE relapse but failed to inhibit the disease relapse if induced at a delayed time point. In correlation, long-term cultured neural precursors lost their capacity to inhibit immune cell proliferation in vitro. Loss of NPC immune functions was associated with transition into a quiescent undifferentiated state. Also, allogeneic foetal NPC grafts elicited a strong immune reaction of T cell and microglial infiltration and were rejected from the host brain. We conclude that long-term functional changes in transplanted neural precursor cells lead to loss of their therapeutic immune-regulatory properties, and render allogeneic grafts vulnerable to immunologic rejection. Thus, the immunomodulatory effects of neural precursor cell transplantation are limited in time

This study looked at the effect of neural stem cells (stem cells that can make nerve and glial cells) to immunomodulate. They could do this when applied early in experimental disease but once disease was established they did nothing as immunomodulators. However, you do not treat MSers before they get MS. Then it says to me that neural stem cells do not immunomodulate and so much of the studies published previously is simply hype. The lab doing this study was one of those leading way to show the immunomodulation by stem cells story and this work suggests that their view will be modified about benefit. However, I think that we should not be expecting them to having dramatic or in fact any immunomodulatory effect in MS. The question is can they become myelin-repair cells? I have viewed much of the so called immunomodulation studies using stem cells with a sceptical eye and this tends to confirm this view. 

Even our own work has not shown nuch immunomodulatory actions of these cells. When it does occur it is usually marginal to what can be achieved with card-carrying immunomodulatory drugs. However we shall see. There are studies with other types stem cells that have also been reported to be immunomodulatory, which are in trial in MS as we speak so we will see what happens.

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