Stem cell transplants applied in conjunction with a protein that stimulates neuron differentiation can repair 'permanent' brain damage in mice
While many kinds of brain injury can occur, one of the most prevalent is an ischemic stroke event, in which a clot blocks blood flow to a region of the brain. Ischemic events make up 87% of all strokes, and affect over 795,000 people in the US alone every year. This can be catastrophic, frequently leaving permanent brain damage as a result. Stem cell therapies could offer a potential solution when applied after a stroke - regenerating starved tissue.
Triggering neuron creation
A research team at USC first discovered a protein called 3K3A-APC, a type of human protein "activated protein C." This appeared to act as a neuroprotectant - stimulating transformation of neural stem cells into neurons. This novel protein is currently being tested by itself in a phase 2 trial on ischemic stroke patients
A dual approach
Following the discovery of 3K3A-APC, the same USC team combined a stem cell transplant at the same time as delivery in mice suffering from stroke damage.
"We showed that 3K3A-APC helps the grafted stem cells convert into neurons and make structural and functional connections with the host's nervous system. No one in the stroke field has ever shown this, so I believe this is going to be the gold standard for future studies"
While stem cell transplantation has been attempted before to some success, there are remaining issues with permanency - as many transplants fail to integrate correctly. 3K3A-APC appeared to act as a neuroprotectant, stabilising and assisting integration of newly differentiated neurons.
"The need for an efficacious, practical and late treatment of stroke remains unmet," Wang said. "Regenerative medicine with stem cells holds great promise for the treatment of stroke. Functional deficit after five weeks of stroke were minimized, and the mice were almost back to normal in terms of motor and sensorimotor functions. Synapses formed between transplanted cells and host cells, so there is functional activation and cooperation of transplanted cells in the host circuitry"
What did the team do?
The researchers tested the combination therapy on mice a week after stroke damage, which is the equivalent of a period of months in humans. They administered 4 doses of 3K3A-APC to the transplant, in addition to an immunosuppressant cyclosporine. In order to confirm the improved motor functions and results they were seeing in treated mice, they also used a targeted toxin to kill these newly formed neurons. This returned the mice back to their previous state, which indicated these new neuronal networks were responsible for the improvement.
In an encouraging previous study from Stanford, some stroke patients injected with adult stem cells actually regained the ability to walk. This was achieved using adult stem cells that assist the brain in the creation of new neurons, but don't actually differentiate themselves. This latest transplant method in combination with a neuroprotectant protein could offer a more potent alternative, although so far the research has only been conducted in mice and we'll need human data to compare efficacy.
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