Study: stem cells implanted in hippocampus restore memory function

  • 22 Apr 2013

A team of neuroscientists has published a paper revealing how it used embryonic human stem cells to trigger neuron growth and repair memory function in mice.

The technique, though aimed at generating models for drug development, is not currently a viable form of therapy for those suffering with neurological disorders such as Alzheimer's. This is partly because we are at the very early stages of testing such treatments, partly because we still know so little about the causes of disorders such as Alzheimer's that it would be too dangerous to transplant stem cells into, potentially, the wrong brain pathway.

The Waisman Centre team behind the study first destroyed an area of the brain known as the medial septum in mice. It's there that cholinergic and GABA neurons -- associated with Alzhemier's and other neurological disorders, from epilepsy to addiction -- connect the medial septum to the hippocampus, which plays a vital role in memory. Cell loss in the hippocampus is one of the first signs of Alzheimer's, demonstrating the vital function cholinergic and GABA neurons play.

Human embryonic stem cells that had been manipulated to become neural progenitor cells -- precursor cells with the potential to become all different types of brain cells -- were then transplanted directly into the hippocampus. The cells were programmed to become cholinergic and GABA neurons, the former of which immediately began to "synaptically connect with endogenous neurons", according to the authors. "In the normal brain, there is a connection between the septum and hippocampus," lead author Su-Chun Zhang told "Now, in this model, this connection is severed. What we did was to place the septum cells (that were produced from stem cells) directly into the hippocampus so that their connections are restored through a short-cut." "These two neuron types are involved in many kinds of human behaviour, emotions, learning, memory, addiction and many other psychiatric issues."

Post-transplant, the mice scored better in traditional memory tests, suggesting the function of the medial septum had been restored, along with improved hippocampus function.

In a statement, Zhang said the key to the study's success was ensuring the regenerated cells were "pure": "In many other transplant experiments, injecting early progenitor cells resulted in masses of cells -- tumours. This didn't happen in our case because the transplanted cells are pure and committed to a particular fate so that they do not generate anything else." This has often been the case when using embryonic stem cells over adult or amniotic, but Zhang insists the danger will always remain unless the introduced cells are rendered pure. "If the adult stem cells can also produce the types of neurons we have shown, they may have similar effects," he told "Regarding the risk of tumours, any type of stem cells, after prolonged expansion in culture, pose a risk of tumour formation. The key issue is whether the stem cells can be directed to the target cell types in an enriched or purified manner, which we have shown."

A July 2012 experiment by US company StemCells garnered similiar results. In it, human neural stem cells were successfully transplanted into the hippocampus of two animal models to restore memory and synaptic function. However, it's unclear whether the cells functioned safely in the brain, producing only the desired cells as with Zhang's study, or whether they went on to over-divide and form tumours.

Zhang comments that with his study, though "it is possible to target the damaged hippocampus for treatment," he did not wish to go as far as calling it an Alzheimer's treatment because "the model we used is not exactly the Alzheimer's model". "[Understanding disorders such as Alzheimer's] is probably the best use of the strategy we have at this moment," he told "If we have stem cells reprogrammed from Alzheimer's patients' blood or skin cells we will be able to examine the cholinergic neurons and GABA neurons from the patient."

The full study is published in Nature Biotechnology.