Potion has magic cell reverse growth

Researchers add "magic potions" to the cells.

How to induce pluripotent stem cells quickly and well, and recently there are new methods. Researchers have developed a set of "magic potions", which in turn use the cells to "bath", which can quickly and well achieve a variety of somatic cell types of "rejuvenation."

After five years of research, the research team led by Yan Duanqing, a researcher at the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, has revealed the scientific principles of chemical methods for preparing stem cells, providing a new scientific perspective and solution for inducing pluripotent stem cell research and optimizing preparation pathways. . The results were published in the International Stem Cell Authoritative Journal Cell Stem Cell.

Using stem cells as "seeds" to develop organ tissues that can replace their own lesions or aging

"Rejuvenation" is a magical word. For thousands of years, many monarchs in ancient and modern China and abroad have been obsessed with it, and modern people are constantly pursuing eternal youth. Nowadays, the “rejuvenation” at the cellular level has become a reality in the laboratory, and the key technology is to prepare stem cells.

So what is a stem cell? In short, stem cells are a type of cell that "changes".

First, it has the ability to self-renew and can divide and maintain the original undifferentiated state in animal embryos and tissues. Secondly, it has the ability to differentiate, that is, the ability to "change". Under different culture conditions, it can become different kinds of cells with different functions. Again, it is a type of cell that is not fully differentiated and is still immature in the primitive stage of cell development.

There are almost all kinds of tissues and organs in our body, such as neural stem cells, hematopoietic stem cells, germline stem cells, mesenchymal stem cells, etc. These stem cells are called adult stem cells because they can only further differentiate into specific types of cells.

"Organic stem cells are like the trunk of a big tree. Embryonic stem cells are equivalent to the roots of that big tree. Embryonic stem cells can not only maintain unlimited self-renewal characteristics, but also can differentiate into various tissue cell types in the body. It has always been considered the most 'Universal cells' with clinical application value.” Yan Duanqing said, “That is to say, under different culture conditions, it can become different kinds of cells with different functions, just like Sun Wukong, want to become beautiful, beautiful, I want to be a handsome guy and become a handsome guy."

Stem cells are a large family, which can be divided into many categories according to different classification criteria. The above-mentioned adult stem cells and embryonic stem cells are only classified according to the source standards of stem cells. According to its developmental level and differentiation ability, it can also be divided into pluripotent stem cells, pluripotent stem cells and unipotent stem cells.

Qi Duanqing said: "All-round stem cells, such as fertilized eggs, are the highest state of stem cells, which can eventually develop into intact individuals and extra-embryonic tissues; pluripotent stem cells, such as embryonic stem cells, are stem cells with unlimited proliferation and multi-directional differentiation potential. Differentiate into all organs and tissues of an individual; unipotent stem cells, such as hematopoietic stem cells, neural stem cells, have only a few closely related cell types that are limited to differentiate."

In short, stem cells are "magic" and can be used in many fields of medicine and basic research. However, the most recent regenerative medicine is the use of stem cells as "seeds" to cultivate organ tissues and the like to replace damaged, self-contained or aging organ tissues.

Through the compound to induce stem cell diversity, a variety of somatic cell types are “rejuvenated”

So how do you get stem cells in the lab? Scientists can obtain stem cells by in vitro isolation and culture. By dedifferentiating somatic cells into pluripotent stem cells by introducing foreign genes, we call them induced pluripotent stem cells.

In 2007, the team of Japanese scientist Yamanaka Yamanaka invented a method of inducing epidermal cells to transform them into pluripotent stem cells. The stem cells induced by this method can be transformed into myocardial and nerve cells, which provides great help for the study of various cardiovascular diseases. This method is known in the industry as "Shanzhong Yanmi Method", and its research results are exempted from the ethical and moral constraints of using human embryos to extract stem cells, and thus are widely used throughout the world. The Yamanaka team also won the 2012 Nobel Prize in Physiology or Medicine.

However, the "Shanzhong method" is still flawed. It uses the viral vector for gene delivery and has a carcinogenic hazard, which poses a greater risk for future clinical applications. Later, some scientists used chemical small molecules to replace the sacral stem cells to induce pluripotent stem cells, but there were shortcomings such as many steps, long time, low efficiency, and unclear mechanism.

After many years of research, the research team led by Prof. Duan Duan developed a highly efficient and simple method for inducing pluripotent stem cells by chemical small molecules, that is, compounds induce stem cell pluripotency.

Yan Duanqing said: "Our program only needs to use the two different 'drugs' in turn to 'bath', so that the somatic cells can be 'rejuvenated' to the state of embryonic stem cells. This method is simpler and more efficient than the previous one. The initial amount of cells required is small. More importantly, a variety of somatic cell types, 'rejuvenation', can be achieved, including hepatocytes that are extremely difficult to culture in vitro."

Provide new directions for drug-induced cell fate transformation and promote the development of regenerative medicine

How do these magical "magic potions" induce adult cells into the state of pluripotent stem cells in the early stages of embryonic development? The study found that the fate of cells is controlled by the state of the "information hub" of the nucleus.

"The sum of the open (1) and closed (0) states of cellular chromatin constitutes the state of determining cell fate. This situation is like a computer binary 'password string', which in turn locks the cell in a specific state." Say.

Further research by the research team found that members of the transcription factor family such as AP-1 and ETS are guarded around the open chromatin site of adult cells, while in embryonic stem cells, they are guarded by transcription factor family members such as OCT, SOX and KLF. . The "rejuvenation" of cells is that the adult cell-specific chromatin is from open to closed, while the stem cell-specific chromatin is from the closure to the open replacement process.

Yan Duanqing said: "Our study is to use drugs to finely regulate the state of the password on the cell chromatin 'cue string'. First, use a group of drugs to 'unlock' the somatic cell fate state, and then use another group of drugs to bind the cells. Destiny drives the state of pluripotent stem cells, which in turn achieves the 'rejuvenation' of cell fate."

Interestingly, the researchers also discovered the puberty of drug-driven cells that “rejuvenate”, that is, drugs that drive cells back to the chromatin intermediates guarded by GATA and FOX transcription factor family members, and then return to similar early embryonic development. The pluripotent stem cell state. This discovery embodies the particularity and ingenuity of drug-driven cell “rejuvenation” in the design of “unlocking” program, and provides theoretical guidance for the application research of drug-induced cell fate transition.

Because no foreign genes were introduced, the compound-induced stem cell pluripotency method of the Qi Duanqing team is simple and easy to operate, and the conditions of the induction process are uniform and standardized. It will provide a safe and efficient method for preparing stem cells for stem cell applications, and has a broad application market. At the same time, it provides a new direction for the development of drugs to induce cell fate transformation, which will greatly promote the development of stem cells and regenerative medicine, and serve the medical and health undertakings in China.

Xie Xin, a researcher at the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences and deputy director of the National New Drug Screening Center, said that the research method is significantly different from the conventional induction method and is a completely new mechanism. Moreover, this study greatly improved the efficiency of induction, making chemical induction promising as a conventional method for inducing pluripotent stem cells. More importantly, this research has made China a world leader in compound-induced pluripotent stem cells.

"In the future, we can design specific potions according to the type of stem cells required, and purposefully induce various stem cells." Yan Duanqing said that this is only the beginning, and further research is being carried out to significantly shorten the "soaking" time of cells and improve efficiency.

Source: People's Daily

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