In a promising new study published in Stem Cell Reports, scientists at Kyoto University in Japan say they've developed a stem cell technique that might one day lead to treatments for Parkinson’s disease.
Using cells taken from a macaque monkey, they created induced pluripotent stem cells (iPSCs), then prompted the cells to grow into nerve cells, called neurons. They injected the new neurons into the same monkey’s brain, where the cells successfully grew and were not rejected by the monkey’s immune system.
Unlike stem cells taken from embryos, iPSCs are made from the subject’s own mature cells by essentially turning back the clock on their development. This means that they share the same DNA as the subject—in this case, a monkey—so the subject’s immune system won’t attack them as if they were foreign invaders.
Previous studies showed that when scientists tried to inject neurons into rat brains, the rats’ immune systems rejected the cells. “But [the immune system] of rodents is not well known and is different from that of primates,” explained Dr. Jun Takahashi, a professor in the Center for iPS Cell Research and Application at Kyoto University, in an interview with Healthline.
A Match Made in the Immune System
As with organ transplants, in order for a stem cell transplant to work, the donor cells must be a match for the patient receiving them. To determine a match, scientists examine a portion of the immune system called the major histocompatibility complex (MHC).
The MHC provides markers on the outside of cells for the immune system to read. It tells immune system defenders which cells are friendly and which are intruders that must be destroyed. If a donor’s MHC is too different from the recipient's, the recipient’s immune system will attack the transplanted cells.
By transplanting stem-cell-grown neurons into various monkeys, Takahashi found that the more different the donor’s MHC was from the recipient's, the more strongly the recipient’s immune system rejected the cells. When he put the neurons into the same monkey they were grown from, the MHC signature was identical, and the monkey’s immune system had a minimal reaction to the new cells.
One major problem for organ transplant recipients is that they have to take immunosuppressant drugs to prevent their immune system from attacking their new organs. As a result, their weakened immune systems can’t fight off infections as easily. Takahashi’s method would allow patients to receive neuron transplants while only having to take a very small dose of these potent drugs.
Promise for Parkinson’s Patients
Once they get the technique working reliably in monkeys, the next step is to develop neuron transplants for humans. “[The] basic structure of the MHC is similar between humans and monkeys,” said Takahashi, suggesting that the monkey research will translate well to humans.
Neuron transplants could be used to treat any number of diseases that damage the brain, including Parkinson’s. In Parkinson’s disease, neurons that produce a substance called dopamine start dying off. Dopamine is responsible for a large number of functions in the brain, including the ability to move one's muscles. As these neurons die, people with Parkinson’s develop tremors and partial paralysis.
Takahashi’s team grew the type of neurons that produce dopamine and implanted them into the putamen, the brain region that gets damaged by Parkinson’s disease. There, the new neurons were able to stabilize and grow.
Many questions must still be answered before this technique is ready for human trials. Neurons form thousands of connections to other cells, and if the new neurons’ connections don't grow properly, they might not work, or could even cause diseases of their own. Diseases like epilepsy and many types of mental illness occur when neurons are present, but are wired up incorrectly.
Still, Takahashi’s team has broken new ground. Someday, Parkinson's could be cured with a simple injection of new, healthy neurons made from a patient’s own cells.