Saturday, 31 August 2013

Electrically Active Stem Cells


Pluripotent stem cells (PSCs) have been differentiated into oligodendroglial progenitor cells (OPCs), providing promising cell replacement therapies for many CNS disorders. Studies from rodents have shown that brain OPCs express a variety of ion channels, and that a subset of brain OPCs express voltage-gated sodium channel (NaV ), mediating the spiking properties of OPCs. However, it is unclear whether PSC-derived OPCs exhibit electrophysiological properties similar to brain OPCs and the role of NaV in the functional maturation of OPCs is unknown. Here, using a mouse embryonic stem cell (mESC) GFP-Olig2 knockin reporter line, we demonstrated that unlike brain OPCs, all of the GFP+ /Olig2+ mESC-derived OPCs (mESC-OPCs) did not express functional NaV and failed to generate spikes (hence termed "non-spiking mESC-OPCs"), while expressing the delayed rectifier and inactivating potassium currents. By ectopically expressing NaV 1.2 α subunit via viral transduction, we successfully generated mESC-OPCs with spiking properties (termed "spiking mESC-OPCs"). After transplantation into the spinal cord and brain of myelin-deficient shiverer mice, the spiking mESC-OPCs demonstrated better capability in differentiating into MBP expressing oligodendrocytes and in myelinating axons in vivo than the non-spiking mESC-OPCs. Thus, by generating spiking and non-spiking mESC-OPCs, this study reveals a novel function of NaV in OPCs in their functional maturation and myelination, and sheds new light on ways to effectively develop PSC-derived OPCs for future clinical applications.

Shiverer mice do not make proper myelin basic protein and develop neurological problems...not surprisingly they shake or shiver. This team have added a sodium channel to the OPC and apparently this makes them better myelinating cells. 

These cells become electrically active and this has been seen before when another molecule called NMDA is introduced. This allows the cells to respond to glutamate, which responds to stimulation with ionic movements in and out of the cells following electrical stimulation of nerves. This allows oligodendrocytes to mature in some peoples hands and not others. 

The electrically active oligodendrocytes can cross talk with nerves. Neurons can no longer be considered the only cells that fire electric impulses in the brain. and Synapses between neurons are not the only way electrical information is regulated as it propagates through neural circuits: oligodendrocytes can cause rapid activity-dependent changes in nerve firing. Nerve impulses can be rapidly regulated by oligodendrocytes. 

Nav1.2 is  developmentally expressed in the nervous system by is not really a feature of nervous expression in adults, which is the domain of Nav 1.6 (There are at least 8 different channel types), however it is found in astrocytes. This study may suggest the importance of stimulating Nav 1.2 but this could have side-effects. May be one can selectively simulate this in oligodendrocytes. 

At present there are studies on the use of sodium channel bloggers in MS and they block Nav1.2. To date there is no evidence to suggest a deterioration. 

However this shows you can engineer stem cells to promote more myelin,we are doing similar things using a differnt approach. However this is some way  away from an option for human use

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