细胞基因治疗,肺部疾病 z-bo 2020-09-16 367

　　Researchers have developed a new cell transplantation method to treat mice that mimic rare lung diseases. One day, this method could be used to treat this and other human lung diseases caused by immune cell dysfunction.

　　Scientists at the Cincitante Children’s Hospital Medical Center reported their discovery in nature on October 1. In this study, the authors used macrophages to collect and remove molecules and cell debris used in the body. We bred to mimic human diseases

　　In hereditary alveolar proteinosis (hPAP) mice, normal or genetically modified macrophages were transplanted into the airways of mice, and both were modified. Mouse disease. Dr. Bruce Trappnell, 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." Cynthanti Children's Hospital Neonatal Science Paper (PMT) as The first special treatment for hPAP children, and Takuji Suzuki from the Pulmonary Biology Department provided support. Suzuki and Trapnell discovered and first reported hPAP in 2008. In hPAP, the alveoli are filled with a surfactant-the lung produces this substance to reduce surface tension and cause alveoli. Keeping it open, children with hPAP have CSFR2RA or CSFR2RB mutations that reduce the ability of alveolar macrophages to remove surfactants from the lungs of these children. Accumulation in the alveoli of these children can cause respiratory distress and respiratory insufficiency. At present, the only treatment for these children is to complete an invasive lung cleaning procedure under general anesthesia. This method is effective, but the effect is temporary and requires frequent surgery, which causes quality problems in sick children. We use bone marrow transplantation (BMT) to test the treatment of hPAP mouse models with severe bone marrow suppression, or use radiation and chemotherapy to destroy the existing bone marrow. BMT is effective in mice. However, in humans, the patient's new bone marrow may die before receiving growth and expansion treatments. Studies have confirmed that it is not necessary to directly regenerate bone marrow-derived cells, and colony-forming macrophages can maintain themselves. Trapnell and Suzuki hope to test a new type of macrophage transplantation therapy, the result of which is natural and healthy macrophages and genetically modified macrophages cell. Has been shown to play a good role in correcting this disease in mice

　　"In mice where the mouse gene Csf2rb loses expression and mimics hPAP, viral vectors are used to transfer the modified Csf2rb gene to animals. Were transported to abnormal alveolar macrophages, and then these genetically modified cells were directly perfused into the lungs of mice

　　Researchers said that this treatment is safe and can meet the needs of animals. Can withstand the mortality of this lung disease, normalize the biomarkers associated with the disease and reduce the disease specificity for at least one year through a treatment. /This gene/cell therapy is very successful in experimental mice, but the author emphasizes that more research and testing is needed before applying this therapy to humans. They still need to determine the exact pharmacokinetics. We also need data to help determine the appropriate dose level and duration of efficacy after treatment. These preclinical trials are currently underway, and the human research program is being planned and designed.