Rewiring the Brain With Stem Cells

Ira Flatow, ScienceFriday.com, January 22, 2010

One of the major questions surrounding stem cell therapy for brain disorders is whether the stem cells actively form functional neurons, or whether they provide an environment suitable for the brain to regenerate itself.  For example, in animal models of stroke, administration of cord blood stem cells is associated with production of new blood vessels, which allow for the brain to heal itself.  In this example the stem cells are acting more as producers of growth factors, as opposed to generating new neurons.  In other experiments, including clinical trials, it was demonstrated that locally implanted stem cells can become neurons, but the extent to which the neurons integrate and work with existing neurons was not completely understood.

Scientists from Stanford examined this problem using embryonic stem cell derived neurons in a recently published paper (Ideguchi et al. Murine embryonic stem cell-derived pyramidal neurons integrate into the cerebral cortex and appropriately project axons to subcortical targets. J Neurosci. 2010 Jan 20;30(3):894-904). 

Embryonic stem cells were grown under special conditions to cause their transformation into neurons that are found in the cerebral cortex.  Once these neurons were transplanted into the mouse they were capable of forming 5 types of brain cells, with projections that extended all the way into the spinal cord.  Interestingly the neuronal projections extended only to cells that normal neurons would have integrated with.  These data support the idea that stem cell derived neurons are capable of forming anatomically correct connections.  The interesting thing about this publication is that the mouse was not injured.  Usually stem cells require some type of tissue injury which causes their homing to the appropriate location.  The publication suggests that various cells of the body naturally produce chemicals that can "guide" new brain cells into forming proper connections. 

One of the problems of embryonic stem cell research has historically been that although the cells are capable of becoming different tissues, the tissues are often formed in a disorganized manner.  The scientists of the current publication demonstrated that an "in vitro education" of the stem cells is capable of programming them to act in a manner that is biologically correct.

Dr James Weinmann, senior author of the publication stated "These stem cell-derived neurons can grow nerve fibers between the brain's cerebral cortex and the spinal cord, so this study confirms the use of stem cells for therapeutic goals."