Cell Stem Cell: Significant progress! Chen Yuejun's team found that transplanting nerve cells from stem cell sources could improve behavioral disorders in the Parkinson's model.

Although cell transplantation can save motion defects in the Parkinson's disease (PD) model, it is unclear whether and how the transplant functionally repairs damaged neural circuits in the adult brain.
September 22, 2020, researcher Chen Yuejun of the Center for Brain Science and Intelligent Innovation of the Chinese Academy of Sciences (Neuroscience Research Institute), Shanghai Brain Science and Brain Research Center, and the Key Laboratory of Primate Neurobiology of the Chinese Academy of Sciences, in collaboration with the Zhou Wenhao/Xiongman Research Group of Fudan University's Affiliated Pediatric Hospital, and the Zhang Suchun Research Group of the University of Wisconsin, USA, published online in Cell Stem Cell. Human Stem Cell-Derived Neurons Repair Circuits and Restore Neural Function's research paper, which analyzed the neurorestructive neural circuits of human dopamine neurons transplanted from mouse brain transplants in Parkinson's disease models, found that nerve cells from transplanted stem cell sources can specifically repair damaged black-styroid loops in the adult brain and improve behavioral disorders in Parkinson's model animals.
neurons are the basic functional units of the brain, we have thousands of different types of neurons in the brain, neurons form complex and precise network connections (neural loops), we perceive the world, thinking and behavior of the basis.
Many neurological disorders, including stroke, brain trauma, and neurodegenerative diseases (Parkinson's disease and Alzheimer's disease, etc.), can lead to the loss of neurons in the brain and the destruction of neural connections, which in turn can lead to severe neurological disorders such as paraplegia, slow movement, muscle stiffness, impaired learning and memory.
However, adult mammals, including humans, have limited capacity for nerve regeneration in the brain, and there is a lack of effective clinical treatment for diseases in which the loss of these neurons leads to damage to neural connections and impaired nerve function.
can replace the function of lost nerve cells in the brain (stem cell therapy) by transplanting stem cell-sourced nerve cells in the brain, is one of the potential treatments.
the key to stem cell therapy for neurological disorders is the repair and functional reconstruction of damaged neural loops, but the precise network connections between neurons in our brains are gradually formed during development, involving complex mechanisms for the growth of nerve fibers.
in adult disease brain environments, it remains unclear whether transplanted nerve cells can grow nerve fibers, bridge "lost" upstream and downstream brain regions, and repair damaged neural loops.
more important is whether this repair is the result of random integration of transplanted cells or a specific repair? What are the mechanisms and principles behind them? These are the key issues that need to be solved urgently in the field of stem cell therapy for neurological diseases.
to these problems, the team studied the feasibility and mechanism of repairing damaged neural loops in nerve cells from stem cell sources transplanted into the adult brain using Parkinson's disease as a model.
Parkinson's disease is the world's second largest neurodegenerative disease with static tremor, muscle strength, slow movement, etc. as the main manifestations, the main reason is the brain's metamorphic brain region of dopamine neurons for sexual loss, resulting in the destruction of nerve connections between the brain region of the physique and the strium brain region, which in turn results in insufficient secretion of dopamine in the stria body, which eventually leads to the patient's motor function disorders.
team members have been working to develop human stem cell neurodifferentiation techniques for different types of neurons, and on this basis have established an efficient method for brain-based dopamine neurons in human stem cell differentiation.
team further genetically labeled human stem cells using gene-editing techniques, allowing them to specifically trace the source of stem cells to human dopamine neurons and their nerve fibers.
team members transplanted genetically labeled human dopamine neurons into the damaged cytokine brain region of Parkinson's model mice, and found that the human dopamine neurons transplanted in the molybic brain region grew a large number of nerve fibers, which grew specifically and extended to their endogenous target area- sethosomes, and the vast majority of neurofibers were projected into the synapses.
article pattern map (pictured from Cell Stem Cell) team members further tracked upstream nerve dominance received by human dopamine neurons in the muscogen transplant using genetic techniques and rabies virus-mediated tracer techniques, and found that transplanted human dopamine neurons received neurodegeneration similar to endogenous dopamine neurons.
study of neuron electrophysiological function found that transplanted human dopamine-energy neurons exhibited electrophysiological properties similar to those of endogenetic mice, and received similar neurotransmitter regulation.
These results show that human dopamine neurons transplanted in parkinson's model mice specifically repaired and reconstructed damaged molybon-staphular neural connections, and that their structure and function were highly consistent with endogenetic neural connections.
Finally, through behavioral testing, the team found that the motor dysfunction of mice in the cell transplant group gradually improved with the extension of transplant time, and through chemical genetics technology to inhibit the activity of transplanted nerve cells, the improvement of motor function in mice disappeared, suggesting that the neurofunctional connections reconstructed by transplanted cells led to the recovery of model mouse behavior.
Interestingly, the team transplanted another type of nerve cell, the human cortical glutamate energy neuron, into the carcology in parkinson's model mice, and the nerve fibers were mainly projected into the cortical and olfactory brain regions, barely projecting to the synth, unable to repair damaged black-streptophic neural loops, and the motor dysfunction of model animals could not be improved, indicating that only certain types of cells could repair specific neural circuits.
the study suggests that damaged neural connections in the adult brain can be repaired structurally and functionally by transplanting nerve cells from stem cell sources, reshaping nerve function.
The study also found that different types of nerve cells have different repair effects on the loop, suggesting that targeted transplantation of specific nerve cells is needed for neurological diseases caused by the loss of different types of neurons.
findings provide new ideas and theoretical basis for the treatment of brain damage and neurodegenerative diseases.
the main types of nerve cells in the human brain can now be obtained efficiently in-body through stem cell neural differentiation technology, the development of stem cell technology will bring new hope for the treatment of many neurological diseases.
Fudan University Affiliated Pediatric Hospital Dr. Xiong Man and Dr. Tao Yexuan of the University of Wisconsin are the first authors of this work, dr. Gao Qinqin of the Center for Brain Science and Intelligent Innovation of the Chinese Academy of Sciences, Master Feng Andy yan Wei have also made important contributions.
research has been supported by the Chinese Academy of Sciences, the Ministry of Science and Technology, the Fund Committee and the Shanghai Science and Technology Commission.
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