细胞基因治疗,动物实验 z-bo 2020-10-19 325

　　Researchers have developed a new type of cell transplantation method to treat mice that mimic rare lung diseases. This method can be used to treat this method and other human lung diseases caused by immune cell dysfunction. They raised mice that mimic human hereditary alveolar proteinosis (hPAP). They transplanted normal or genetically modified macrophages into the respiratory tract of mice, both of which were modified.

　　The lead author of the paper, Dr. Bruce Trapnell from the Department of Neonatal Science and Lung Biology, Cincinnati Children's Hospital, said: "The potential importance of these key findings goes beyond the treatment of rare lung diseases. Our findings are lung macrophage transplantation (PMT). ), this is the first case of hPAP children."

　　The results of the "

　　" study also determined the mechanism that regulates the number and phenotype of alveolar macrophages. "The first author of the paper, Dr. Takuji Suzuki, Department of Neonatal Science and Lung Biology, Cincinnati Children's Hospital.

　　Suzuki and Trapnell discovered hPAP in 2008 and reported on it for the first time. In hPAP, the alveoli are filled with surfactant-the lung produces this substance to reduce surface tension and keep the alveoli open. There are mutations in CSFR2RA or CSFR2RB in children with hPAP. These mutations reduced the ability of alveolar macrophages to remove surfactant from the lungs of these children. Surfactants accumulate in the lungs and fill alveolar vesicles, causing respiratory distress and respiratory distress. The only current treatment for these children is to complete an active lung cleansing procedure under general anesthesia. Although this method is effective, the effect is temporary and requires frequent operation, which brings problems to the quality of life of affected children. In some previous studies, bone marrow transplantation (BMT) was used to treat hPAP mouse models with severe bone marrow suppression, or radiotherapy and/or chemotherapy were used to destroy existing bone marrow. I tested that BMT is effective in mice, but in humans, it can cause death, and then treat the patient's new bone marrow to grow and expand. Studies have confirmed that bone marrow-derived cells do not need to be regenerated directly, so that the colony-forming macrophages can maintain themselves. Trapnell and Suzuki hope to test a new type of macrophage transplantation therapy. The results show that natural and healthy macrophages and genetically modified macrophages can also correct this disease in mice. In mice where the mouse gene Csf2rb has lost expression and mimics hPAP, the researchers used viral vectors to deliver the modified Csf2rb gene to the animals’ abnormal alveolar macrophages. These genetically corrected cells were then directly perfused into the lungs of mice. The researchers found that this treatment is safe, well tolerated in animals, and can correct the lung disease with a single treatment, normalize the biomarkers associated with the disease, and can cause the disease for at least one year. Mortality reports say it can reduce specificity. This gene/cell therapy has been very successful in experimental mice, but the author emphasizes that more research and testing are needed before applying this therapy to humans. They still have to determine the exact pharmacokinetics. We also need data to help determine the appropriate dosage level and shelf life after treatment. These preclinical studies are currently underway, and the human research project is being planned and designed.