On April 28th, the medical network usually said that "cerebral infarction" and "stroke" are first aids for life and death. In the future, the treatment of cerebral infarction may not need to race with time. Recently, Guangzhou doctors released the latest research results of the treatment of cerebral infarction: the neural stem cells modified by nanomaterials were transplanted to the infarct, and the brain tissue neurons were "regenerated". The ingenious imaging agent injection design also allows the transplanted neural stem cells to be monitored at any time.
Recently, Shen Jun, a research group of Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, released a new research report on the treatment of cerebral infarction in the advanced journal of Advanced Materials in the field of international materials: directional transplantation of nano-material-modified neural stem cells into infarction Let the brain tissue neurons "regenerate", so that patients with cerebral infarction can be more "comfortable". According to reports, this achievement provides a new method for improving the therapeutic effect of neural stem cells, which helps to promote the treatment of neural stem cells to treat cerebral infarction as soon as possible. The study is currently in the animal experiment phase and is expected to enter clinical trials and applications in China after 3 to 5 years.
Shen Jun, director of the Department of Radiology at Sun Yat-sen Memorial Hospital of Sun Yat-sen University, said that the treatment of cerebral infarction has always been a clinical problem. The pathogenesis of cerebral infarction is that the thrombus blocks the blood supply artery of the brain, causing blood supply disorders in the brain tissue, causing ischemia and hypoxia of the brain tissue. Necrosis of necrosis, death of neurons and glial cells, and the corresponding neurological dysfunction, such as common facial paralysis, quadriplegia, etc., can directly lead to death.
The medical community believes that thrombolysis is the best choice for the rapid and effective treatment of cerebral infarction, and the most effective treatment is in the early stage of the disease. Intravenous drug thrombolysis is the safest and most effective within 3 hours after the onset of cerebral infarction. If more than 3 hours, the neurons in the cerebral infarction area die rapidly, the effect of thrombolytic therapy is poor, and it is easy to cause bleeding in the cerebral infarction area. At present, only about one-third of patients with cerebral infarction at home and abroad can reach the hospital within 3 hours of onset, and only a few can get timely thrombolytic therapy.
After the acute phase, the treatment of cerebral infarction mainly uses some brain protection drugs. In the chronic phase, rehabilitation and acupuncture are mainly used to recover the function of the residual limbs. The effect is very limited. At present, 70% to 80% of patients with cerebral infarction in China cannot live independently because of disability, which requires long-term care and imposes a heavy burden on society and families.
　　 "regeneration" brain tissue neurons
Break through treatment time window limit
Shen Jun introduced that the researchers are committed to transplanting neural stem cells into the cerebral infarction area, through cell proliferation and differentiation, "regeneration" of new neurons, reconstruction of the neural circuit, thereby repairing neurological dysfunction caused by cerebral infarction, replacing damage or death. The nerve cells use this method instead of the traditional thrombolytic therapy to rescue the original neurons, thus breaking the limitation of the treatment time window.
However, in previous experiments, neural stem cells did not differentiate into neurons as expected in the infarcted brain tissue after transplantation, and acted as a substitute for dead neurons. Shen Jun's group found that in animal models, neural stem cell transplantation has a good effect on cerebral infarction, but preliminary clinical trials show that although neural stem cell therapy is safe, the effect on the human body is not as obvious as in animal experiments. The whereabouts after being injected into the brain are also less controlled and often do not remain "obedient" in the area of ​​cerebral infarction.
According to experts, this is mainly because the necrotic brain tissue at the cerebral infarction releases a large number of inhibitory factors, binds to the NgR protein on the neural stem cells, inhibits the differentiation of neural stem cells into neurons, and has no basic unit of neurons. Reconstruction, neurological dysfunction can not be repaired.
Research to develop "nano ping-pong" transformation of neural stem cells
In response to the above problems, Shen Jun's group first tried to design a gene coding sequence (small interfering RNA) that could interfere with this inhibition, and then developed a very tiny table tennis capsule with special nanomaterials and biomaterials. bubble. A small negative interfering RNA with a negative charge is adsorbed by the positive charge on the surface of the vesicle, and then the imaging agent particles are mounted inside the vesicle. These particles act like a single magnet and emit signals in a magnetic resonance imaging machine to enable the neural stem cells to Was directly seen.
Subsequently, these "table tennis balls" with a positive charge on the surface of only about 200 nanometers, close to the neural stem cells, can be efficiently phagocytized within 5 hours. Using this ingenious design, imaging agents and small interfering RNAs are simultaneously transported into neural stem cells, which not only interfere with the binding of inhibitors and NgR, but also promote the differentiation of neural stem cells into neurons. Imaging agents can also enable neural stem cells to be transplanted to designated cells. After the location, its distribution and migration flow can be observed in real time.
Effect "upgrade" six times higher neural stem cell efficiency
The research team used magnetic resonance imaging to perform real-time and accurate tracking to ensure accurate delivery of stem cells to the infarct area, and to directly see the distribution and movement of neural stem cells while the animals are alive.
The test results show that after the "upgraded" neural stem cells treated by this table tennis-like vesicle, after transplanting into the cerebral infarction area, the proportion of differentiation into neurons in the complex environment of animal cerebral infarction can be increased from about 4% to about 27%. , increased by about 6 times. The results also showed that accept the "upgrade" neural stem cells transplanted animal, limb motor and sensory dysfunction than untreated transplanted neural stem cells to recover faster and better.
Shen Jun said that this nano-table tennis table, which combines tracer and function regulation, has great application prospects in cerebral infarction regenerative medicine. It is expected to enter the clinic after three to five years.