While mentioning the incurable disease, we usually consider the cancer-related disease. However, cardiovascular diseases is on the top chart, and WHO also offered the same ranking! In the field of cancer, tumor immunotherapy recently made a major breakthrough, which will be applied to control some sort of cancer become a chronic disease. But for the field of cardiovascular disease treatment, still, need such a breakthrough. In this post, we will share a study posted on Proceedings of the National Academy of Sciences (PNAS) that introduced the derivation of functional arterial endothelial cells for clinical application from human pluripotent stem cells.
For cardiovascular diseases patients, one of the commonly used treatment methods is to implement Heart Bypass Surgery. In the course of surgery, doctors often need to operate venous graft for patients. However, not all the vein of patients can be applied for Heart Bypass Surgery due to the disease and age factors. Currently, stem cells field made astounding advances, many scientists start to consider the possibility to induce artery in vitro for Heart Bypass Surgery. With the development of science in this field, scientists have been able to induce ordinary vascular endothelial cells in vitro. This definitely is a big step, but still, need more progress for clinical application.
For figuring out the solutions to induce Radial Artery in vitro to apply for Heart Bypass Surgery, scientists began to research how the arterial cells formed in natural condition. Researchers isolated endothelial cells from arteries and veins in mouse embryos, and then utilize single-cell RNA sequencing technology which is the recent popular technology to find those signal pathways that play a key role in the arterial endothelial cell differentiation. The results of this experiment prove to be highly successful, researchers found 42 related genes in all. And all these genes are related to growth factors which suggest that the differentiation of arterial endothelial cells is regulated by these growth factors.
To further validate this hypothesis, the researchers used another cutting-edge technology - CRCIS gene editor, to produce a human embryonic stem cell line for the next phase of experiments. In an embryonic stem cell line, the researchers introduced red fluorescence to identify arterial endothelial cells; and a green fluorescence to identify venous endothelial cells in the other cell line. Subsequently, they add or remove different growth factors and other small molecules in the culture dish to regulate these newly discovered pathways. Researchers confirmed the effect of the single growth factor on arterial endothelial cells by comparing the expression of TOM and EGFP.
Some incredible data was found with this study - insulin and other common growth factors will inhibit the differentiation of arterial endothelial cells in the field of stem cells. The study team eventually developed a new induction technology to induce the production of arterial endothelial cells with 5 key growth factors. So what is the difference between these induced cells and the natural cells? Researchers found that they did express some of the key genes in arterial endothelial cells, which reflected their differences with ordinary endothelial cells, and the other feature is that these cells will produce more nitric oxide and consume more oxygen than intravenous endothelial cells which is identical to native coronary arteries.
The final aim for this study is for clinical application, researchers claimed that they wish this technology can be used to promote the formation of functional arteries as this study proved that we can reliably obtain functional arterial endothelial cells and produce artificial arteries similar to natural arteries. Also, they will devote to further develop these cell line and bring the generic arteries. Once come true, there will be a revolution in cardiovascular diseases treatment!