Dopaminergic neurons produced by transplantation of human stem cells are expected to treat Parkinson's disease

  After being injured by trauma, stroke or degenerative disease (such as Parkinson's disease), the mature brain has very poor function in self-repair. Stem cells with unlimited adaptability provide hope for better nerve repair. However, the complexity of precise coordination of the brain hinders the development of clinical treatments.

  New research aimed at overcoming these obstacles includes researchers from the University of Wisconsin-Madison, the Chinese Academy of Sciences Center for Excellence in Brain Science and Intelligent Technology, the Chinese Academy of Sciences, the Shanghai Brain Science and Brain-like Research Center, and researchers from Duke University to the National University of Singapore School of Medicine It has been demonstrated that stem cell therapy can prove this concept in a mouse model of Parkinson's disease. They found that neurons produced by human embryonic stem cells (ESC) have successfully integrated into the correct areas of the brain, established connections with these endogenous neurons and restored motor function. By carefully tracking the fate of the transplanted stem cells, these authors discovered the identity of these cells in dopamine-producing neurons in Parkinson's disease (that is, dopamine-producing neurons, also called dopaminergic neurons). )---Determine the connections and characteristics they generate. With the increasing use of stem cells to generate dozens of unique neurons, this study shows that neural stem cell therapy is a viable goal. However, further research is needed to convey the results of the mouse study to humans. Zhang Suchun, a neuroscientist at the University of Wisconsin-Madison, said: "Our brains are precisely connected to very specific nerve cells in specific locations and can perform all complex movements. Everything depends on it. Specific cell types. Formed by connecting neural circuits. Neural circuits, nerve damage usually affects specific brain areas or specific cell types, thereby destroying neural circuits. Neural circuits need to be repaired."

  To repair these neural circuits in a mouse model of Parkinson's disease, dopamine-producing neurons will die of Parkinson's disease, so these authors first converted human embryonic stem cells into dopamine-producing neurons. Induce differentiation. They transplanted these newly generated neurons into the midbrain of these mice, which is the brain area most affected by Parkinson's degeneration. After a few months, these newly generated neurons had time to integrate into the brain, and then the motor skills of these mice improved. Through careful observation, Zhang and his team were able to observe that these transplanted neurons extend a long distance and are connected to the motor control areas of the brain. They also establish contact with the regulatory regions of the brain that enter new neurons and prevent them from being overstimulated. The connection between the input and output of these two groups of transplanted neurons is similar to the neural circuit established by endogenous neurons. This only applies to neurons that produce dopamine. Similar experiments were performed using neurons that produce the neurotransmitter glutamate, which is not involved in the development of Parkinson's disease. The results showed that the transplantation of these glutamate-producing neurons could not repair the motor circuits of these mice, and the importance of neuron identity repairing damage. In order to finally prove that these transplanted dopamine-producing neurons repaired neural circuits damaged in Parkinson's disease, these researchers inserted a switch gene into human embryonic stem cells. It is achieved that when these cells are exposed to specially designed drugs in the diet or through injection of drugs, these on/off switches will increase or decrease the activity of these cells. When these stem cells were turned off, the improvement in the exercise capacity of these mice disappeared, indicating that these stem cells are essential for restoring the brain caused by Parkinson's disease. New research also shows that the gene conversion technology can be used to fine-tune the activity of transplanted cells to optimize treatment.

  Over the years, Zhang's research team and other researchers have developed methods to transform stem cells into different types of neurons in the brain. Each neurological disease or injury requires its own specialized nerve cells for treatment, but the treatment plan can be similar. Zhang said: "We use Parkinson's disease as a model, but the principles are the same for many different neurological diseases."

  This research has personal significance to Zhang. As a doctor and scientist, he often receives letters from families eager to treat neurological diseases or brain injuries. This is also an experience he can sympathize with. Six years ago, Zhang broke his neck in a bicycle accident. He was half paralyzed when he woke up in the hospital. The first thing he thought of was stem cells-he has been studying for many years-how it can help his recovery.

  After years of physical therapy, Zhang still believes that the right stem cell therapy may help people like him and the family he will hear in the future.

  For this reason, Zhang's team is currently testing similar treatments for primates. This is the first step towards human clinical trials. He said: "There is hope, but we need to take steps gradually."