Jun 212012
 

Dementia is fundamentally a problem of lost neurons (brain cells) and their connections (synapses). A strategy that RNG is therefore exploring is to try to replace this missing brain machinery. But how? One possibility is through the transplantation of Neural Stem Cells directly into the brain.  So called “cell therapy” has received a lot of attention but it remains unknown whether this approach can reverse memory dysfunction, a devastating component of neurodegenerative disorders.  For the first time, RNG researchers explored stem cell therapy in aged rats with memory dysfunction and found that this new treatment restored memory back to normal and made a huge positive effect on brain connectivity.

This research was only possible by a highly specialized technique developed by RNG researchers for generating skin-derived neural precursors (SKINPS). Aged rats were first tested for memory deficits (Rodent Recognition Memory) and then had SKINPS transplanted into their hippocampus (an important brain structure for learning and memory).  Eight weeks later memory tests were repeated to find out if the treatment had been beneficial.

Our results so far are very promising. We found that SKINP cells not only survived in the brain for over 2 months, but migrated throughout the hippocampus and showed evidence of growing into mature neurons (see Figure below).

Confocal image of rodent hippocampus 8 weeks after transplantation. Yellow colour identifies donor SKINP cells that have matured into neurons – a combination of green fluorescence (SKINP marker) overlaid on red fluorescence (neuronal marker).

 

 

 

 

 

 

 

 

 

 

 

 

SKINP transplantation also reverses the profound decline in synaptic numbers associated with ageing. Most importantly, this treatment restores memory of aged rats back to the normal level seen in young rats (Figure below).

 

 

 

 

 

 

 

 

 

 

 

Our findings provide the first exciting evidence that skin-based stem cell based therapy may offer a viable approach for the treatment of common neurodegnerative disorders and memory dysfunction. However, these results are only based on rodents, a poor substitute for the complexity of the human brain. We are therefore about to start on a similar study in dogs with Canine Cognitive Dysfunction, a more faithful dementia model. This research is therefore just a stepping-stone towards possible future human clinical trials.

 For more information contact Joyce Siette on jsiette@psy.unsw.edu.au.