Dopaminergenic Neurons Transplanted into Mouse Brains Integrate Into Neural Circuits and Improve Parkinson's Symptoms
Researchers here demonstrate that human dopaminergenic neurons, the class of cell lost in Parkinson's disease, can integrate into neural circuits and improve motor function when transplanted into mice. The challenge with all such cell therapies, in which cell replacement and consequent functional improvement is the goal, is that it is very hard to achieve any significant survival of cells following transplantation. Finding the right methodology has been a challenge, so proof of concept work like this is more important for the precise details of the methodology used - not discussed here - than for the outcome.
Researchers demonstrated a proof-of-concept stem cell treatment in a mouse model of Parkinson's disease. They found that neurons derived from stem cells can integrate well into the correct regions of the brain, connect with native neurons and restore motor functions. The key is identity. By carefully tracking the fate of transplanted stem cells, the scientists found that the cells' identity - dopamine-producing cells in the case of Parkinson's - defined the connections they made and how they functioned. Coupled with an increasing array of methods to produce dozens of unique neurons from stem cells, the scientists say this work suggests neural stem cell therapy is a realistic goal.
To repair damaged neural circuits in the Parkinson's disease mouse model, the researchers began by coaxing human embryonic stem cells to differentiate into dopamine-producing neurons, the kind of cells that die in Parkinson's. They transplanted these new neurons into the midbrains of mice, the brain region most affected by Parkinson's degeneration. Several months later, after the new neurons had time to integrate into the brain, the mice showed improved motor skills. Looking closely, researchers were able to see that the transplanted neurons grew long distances to connect to motor-control regions of the brain. The nerve cells also established connections with regulatory regions of the brain that fed into the new neurons and prevented them from being overstimulated.
Both sets of connections - feeding in and out of the transplanted neurons - resembled the circuitry established by native neurons. To confirm that the transplanted neurons had repaired the Parkinson's-damaged circuits, the researchers inserted genetic on-and-off switches into the stem cells. These switches turn the cells' activity up or down when they are exposed to specialized designer drugs in the diet or through an injection. When the stem cells were shut down, the mice's motor improvements vanished.
Link: https://news.wisc.edu/stem-cells-can-repair-parkinsons-damaged-circuits-in-mouse-brains/