Release date: 2017-07-12
The most deadly disease in the world? Speaking of this problem, the first reaction in many people's minds may be cancer. This is normal – cancer has attracted a lot of social attention: the healing story of cancer patients is widely spread as positive energy, and the progress of cancer research has also allowed us to see the light of human wisdom.
However, cancer can only rank second in the "most deadly disease list" of humans. At the top of the list is cardiovascular disease. According to the American Heart Association, one in three Americans die each year from cardiovascular disease, and the total number of deceased exceeds the sum of all cancer deaths. The World Health Organization also gives the same ranking.
Why do so many people die of cardiovascular disease every year? There are many reasons behind it, but one of the reasons is that it is too difficult to treat. In the field of cancer, tumor immunotherapy has recently made a major breakthrough, turning some patients' cancer into a chronic disease that can be controlled. In the field of cardiovascular disease treatment, such breakthroughs are still coming.
Today, a study published in the Proceedings of the National Academy of Sciences (PNAS) may be a breakthrough we are waiting for. The first author of the study was Professor Jue Zhang of the Morgridge Institute, and the co-author was Professor James Thomson, the big cow in the stem cell field. The latter is also the first scientist to bring human embryonic stem cells. This team first induced functional arterial endothelial cells and is expected to be applied to the human body.
The topic first returns to cardiovascular disease. Cardiac bypass surgery is one of the most common treatments for many patients. Some data show that between 2001 and 2006, in the United States alone, there were as many as 430,000 coronary artery bypass surgeries and more than 1,000 surgeries per day. During the operation, doctors often need to transplant a patient's veins. However, due to factors such as disease and age, not all patients can be used for bypass surgery. In the current field of stem cell leaps and bounds, many scientists have begun to consider the possibility of inducing arteries to bridge in vitro.
With the development of science, people have been able to stably induce normal vascular endothelial cells in vitro. Although this is a breakthrough, there are still many distances from clinical applications. "These vessels lack the characteristics of the arteries, so the clinical application value is extremely low," Professor Zhang said.
Is there a way to induce an arterial blood vessel for heart bypass directly in vitro? To answer this question, researchers first need to understand how arterial cells form under natural conditions. In mouse embryos, the researchers isolated endothelial cells from arteries and veins, and then used the popular technology of recent years, single-cell RNA sequencing technology, to find those signaling pathways that play a key role in the differentiation of arterial endothelial cells. The power of this new technology enhances the accuracy of the results.
The results of this experiment seem to be very successful – the researchers found a total of 42 related genes, all of which are related to growth factors. This suggests 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, the CRISPR gene editor, to create a human embryonic stem cell line for the next phase of the experiment. In an embryonic stem cell line, researchers introduced red fluorescence that identifies arterial endothelial cells; in another embryonic stem cell line, researchers introduced green fluorescence that identifies venous endothelial cells. Subsequently, they added or removed different growth factors and other small molecules in the culture dish to regulate these newly discovered pathways.
"Using this technology, we can test the function of these candidate genes and assess how many cells can develop into the desired arterial cells," Professor Zhang said.
The study found some striking data – in the field of stem cell science, some common growth factors such as insulin inhibit the differentiation of arterial endothelial cells, which is very surprising. Through continuous exploration, the team eventually developed a new induction technology. As long as five key growth factors are used, the production of arterial endothelial cells can be effectively induced.
So, what is the difference between these induced cells and natural cells? First, the researchers found that they did express some of the key genes in arterial endothelial cells, reflecting their differences from normal endothelial cells. Second, these cells produce more nitric oxide and consume more oxygen than vein endothelial cells. These key data are identical to native coronary cells. These data indicate that these induced arterial endothelial cells are physiologically distinct from normal cells.
But the researchers did not satisfy themselves. Their ultimate goal is to apply this technology to the clinic. In this study, they constructed a mouse model of myocardial infarction and injected the induced arterial endothelial cells into mice. The survival rate of these mice was as high as 83%, which was significantly higher than 33% of the control group. Interestingly, survival was also improved in mice injected with venous endothelial cells. In this regard, the researchers explained that arterial endothelial cells and venous endothelial cells repaired the arterial and venous portions of the mouse model, respectively.
"Our ultimate goal is to apply this cell-inducing technique to promote the formation of functional arteries. We hope to apply these arteries to cardiovascular surgery," Professor Thomson said. "This work confirms that we can reliably obtain Functional arterial endothelial cells and produce artificial arteries that behave like natural arteries."
"Most of the cardiovascular disease's deaths are due to arteries being affected. However, no one has ever been able to make these cells. Our key findings have brought functional arterial endothelial cells. They are clinically useful." Professor Zhang said.
In the future, the team will further develop these cell lines and try to bring general-purpose arteries that are easy to obtain and are not rejected by patients. If this day comes, it will undoubtedly be a revolution in the treatment of cardiovascular disease.
Reference material
[1] Functional characterization of human pluripotent stem cell-derived arterial endothelial cells
[2] Stem cell advance brings bioengineered arteries closer to reality
Source: Academic Jingwei
ZHEJIANG SHENDASIAO MEDICAL INSTRUMENT CO.,LTD. , https://www.sdsmedtools.com