Gene editing "promotes" high-quality human vascular cells

Team Liu Guanghui of the Institute of Biophysics of the Chinese Academy of Sciences, by targeting and editing a single longevity gene, FOXO3, obtained human vascular cells that fight cell aging and cancer, and are expected to be used in the treatment of vasodytic diseases. The findings were published online January 18 in Cell-Stem Cells.
embryonic stem cells originated in the embryonic period. It can not only replicate itself for a long time, but also has the potential to differentiate to form various tissue cells in the human body.
by controlling the differentiation of human embryonic stem cells, damaged and "retiring" tissue cells can be repaired or replaced to treat a variety of diseases, including myocardial infarction, diabetes, bone marrow cell disease, and geriatric degeneration.
, however, stem cell therapy techniques also have limitations in terms of effectiveness and safety. If injected into the body, it is vulnerable to attacks from micro-environments such as disease and aging. These "unsothy" stem cells will soon disappear into the body. Even if there is tenacious survival, it may mutate into tumor cells due to unstable genomes, creating a safety risk in cell therapy.
to help stem cells work better, Liu Guanghui's team solved both challenges using gene editing methods.
researchers first replaced two single nucleotides in the no. 3 exon of the FOXO3 gene in human stem cells using gene editing techniques mediated by the third-generation adenovirus vector HDAdV, which inhibited the phosphorylation and degradation of FOXO3 proteins in cells, promoted the accumulation of FOXO3 in the nucleus, and improved the transcription activity of the gene. It is also differentiated into vascular endothial cells (vascular endometrials), vascular smooth muscle cells (vascular membranes) and interstial cells (vascular exosomes).
blood vessels are like crisscrossing roads in the body, and the transport of nutrients depends on these roads. If roads age, are always congested, and blood is not delivered to organs in time, organs will soon "strike".
these genetically enhanced human vascular cells are like armed soldiers, improving combat effectiveness and adapting to harsh conditions in the "battlefield" and ready to support aging-damaged cells in the body.
blood flow to the legs was blocked after the aorta blood vessels in the legs of mice used in the experimental study were man-made. Injecting genetically enhanced blood vessel cells into the legs is the equivalent of introducing a powerful foreign aid force. Compared with those wild cells in the control group that have not been genetically enhanced, this foreign aid has a stronger ability to self-renew, resist oxidative damage and delay cell aging, which can effectively promote the regeneration of damaged blood vessels and quickly restore blood flow in isoemia sites.
in terms of mechanism, endo-activated FOXO3 mediates resistance to vascular cell aging through antagonist CSRP1 gene expression.
researchers also imported a variety of cancer-causing genes into genetically enhanced vascular cells and found that they were also effective in fighting cell malignant transformation induced by cancer genes, greatly reducing the safety risks of using these cells for treatment.
" our study conceptually demonstrated the feasibility of using gene editing strategies to obtain high-quality and safe human vascular cells. In the future, this strategy may be used to treat atherosclerosis, myocardial infarction, isotromic stroke, diabetic foot, retinal vascular lesions, and other vascular-damaged diseases. Liu Guanghui said. (Source: Li Chenyang, China Science Journal, Liu