Friday, 21 September 2012

Research: Protection using remyelinating schwann cells

EpubZujovic et al. Evercooren AB. Exogenous schwann cells migrate, remyelinate and promote clinical recovery in experimental auto-immune encephalomyelitis. PLoS One. 2012;7(9):e42667. Epub 2012.

Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons in the chronically inflamed CNS. To address this question we investigated the fate of transplanted SCs in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in the Dark Agouti rat; an animal model that reproduces the complex inflammatory demyelinating immunopathology of MS. We now report that SCs expressing green fluorescent protein (GFP-SCs) allografted after disease onset not only survive but also migrate to remyelinate lesions in the inflamed CNS. GFP-SCs were detected more frequently in the parenchyma after direct injection into the spinal cord, than via intra-thecal delivery into the cerebrospinal fluid. In both cases the transplanted cells intermingled with astrocytes in demyelinated lesions, aligned with axons and by twenty one days post transplantation had formed P zero protein immunoreactive internodes. Strikingly, GFP-SCs transplantation was associated with marked decrease in clinical disease severity in terms of mortality; all GFP-SCs transplanted animals survived whilst 80% of controls died within 40 days of disease.

Schwann cells myelinate peripheral nerves (PNS) in a one schwann cell to one nerve ratio. Oligodendrocytes myelinate central nervous (CNS) system nerves in a ratio of one oligodendrocyte to many nerves. Following demyelination insome instances schwann cells can migrate into the CNS and promote remyelination and if you look in lesions in EAE and MS, it is clear that schwann cells can migrate into the central nervous system and myelinate previosuly demyelinated axons. This is easy to see because CNS myelin looks different to PNS the two myelins look diifferent and peripheral nerve contains P0 (p zero) and P2 in the myelin. So when transplanted there was survival of animals. This is great..trying not to sound jaded :-)

                         Schwann cells (green) P0 myelin (Red)

If you want the more jaded side...I will not go on about the ethics of using a model that is so severe where death is an acceptable point of assessment, there should be endpoints before this happens., but this study transplanted cells into animals with EAE and there was greater survival and there was some remyelination that was evident after 3 weeks.

Is the remyelination causally related to survival?, maybe, maybe not, maybe they are producing protection factors that is limiting damage. Indeed we know that putting a needle into nervous tissue can create nerve survival factors. The necessary data is not present to discern this.

However now the problem. There has already been a clinical trial of Schwann cell transplantion in MS in Yale, USA and this study I believe was abandoned. Why? it is not clear because I don't think it was published......maybe you know why or if it is published where? Maybe they could not find any cells, improvement or there was worsening or some adverse effect. Technology has moved on since the trials but I am not sure of the fine details of the trials to comment.

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