Researchers add "magic potions" to cells.

Photo courtesy Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences

How to quickly and well induce pluripotent stem cells has recently been approached. Researchers have developed a "magic potion" that can be used to "bath" cells in turn, and can quickly and easily achieve "rejuvenation" of many somatic cell types.

The research team led by Yan Dingqing, a researcher of the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, after five years of research, revealed the scientific principle of chemical methods for preparing stem cells, and provided a new scientific perspective and solution for inducing research on pluripotent stem cells and optimizing preparation methods. . The related results were published on the International Stem Cell Authority Journal Cell Stem Cell.

Using stem cells as "seeds" to produce organ tissue that can replace autologous lesions or aging

"Rejuvenation" is a magic word. For thousands of years, many emperors and emperors of ancient and modern times have been obsessed with it. Modern people are constantly pursuing youth forever. Today, cell-level "rejuvenation" becomes a reality in the laboratory. The key technology is to prepare stem cells.

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

First, it has the ability to self-renew, can always split in animal embryos and tissues and maintain the original undifferentiated state. Second, 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. Third, it is a kind of immature cells that are still in the primitive stage and have not fully differentiated during cell development.

Almost all kinds of tissues and organs in our body contain stem cells, such as neural stem cells, hematopoietic stem cells, reproductive 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.

"Adult stem cells are like trunks of big trees. Embryonic stem cells are equivalent to the roots of big trees. Embryonic stem cells not only maintain unlimited self-renewal properties, but they can also differentiate into various types of tissue cells in the body. They have been considered the most The “Ultracellular Cells” with clinical application value.” Kuang Duanqing said, “In other words, under different culture conditions, it can become different kinds of cells with different functions. Just like the Sun Wukong, you want to change beauty into beauty. Want to be handsome and become handsome."

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

Qi Duanqing said: "Totipotent stem cells, such as fertilized eggs, are the highest state of stem cells. They can eventually develop into complete individuals and extraembryonic tissues; pluripotent stem cells, such as embryonic stem cells, are stem cells with infinite proliferation and multilineage differentiation potential. Differentiates into all organs and tissues of the individual; unipotent stem cells, such as hematopoietic stem cells, neural stem cells, have only a few closely related cell types that differentiate into a limited number."

In short, stem cells are "supernatural" and can be used in many fields of medicine and basic research. However, the closest thing to reality is regenerative medicine, which uses stem cells as the "seed" to cultivate organ tissues, etc., to replace damaged, self-lesioned or aged organs.

Inducing Stem Cell Diversity Through Compounds, Realizing Multiple Somatic Cell Types

So how can we get stem cells in the laboratory? Scientists can get stem cells by in vitro isolation and culture. The somatic cells are dedifferentiated into pluripotent stem cells by introducing an exogenous gene. We call this type of stem cells induced pluripotent stem cells.

In 2007, a team of Japanese scientist Yamanaka Yamanaka invented a method to induce epidermal cells to transform into pluripotent stem cells. The stem cells induced by this method can be transformed into myocardium and nerve cells, providing tremendous help for the study and treatment of various cardiovascular incurable diseases. This method has been referred to by the industry as the "Yamanaka Yamanaka method." Its research results have been exempted from the ethical and moral constraints of the use of human embryos to extract stem cells, and are therefore widely used throughout the world. Yamagata Shinya team also won the 2012 Nobel Prize in physiology or medicine.

However, there is still a flaw in the “Yamanaka Yamanaka method”. It is the use of viral vectors to carry out gene delivery and has potential cancer-causing hazards, which poses greater risks for future clinical applications. Later, some scientists used chemical small molecules to replace pluripotent stem cells in the mountains to induce pluripotent stem cells, but they have many disadvantages such as many steps, long time, low efficiency, and unclear mechanism.

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

Yan Duanqing said: "Our solution only requires the cells to use two different 'drugs' in turn to 'bath' and then we can 'rejuvenate' somatic cells to the state of embryonic stem cells. This method is simpler and more efficient than previous solutions. The initial amount of cells needed is less, and more importantly, a variety of somatic cell types can be achieved, including hepatocytes that are extremely difficult to culture in vitro.”

To provide a new direction for drug-induced cell fate transformation and promote the development of regenerative medicine

How do these magical “magic potions” induce adult cells to 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 center” chromatin inside the nucleus.

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

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

Yan Duanqing said: “Our study is precisely using drugs to fine-tune the password state on the cytochrome 'password string'. First, we use a group of drugs to 'unlock' the somatic fate state, and then use another group of drugs to Fate drives the state of pluripotent stem cells, which in turn enables the 'rejuvenation' of cell fate."

Interestingly, the researchers also discovered the puberty of drug-driven cells "rejuvenate", in which drugs first drive cells back to the chromatin intermediates guarded by members of the GATA and FOX family of transcription factors, and then return further to something like early embryonic development. The pluripotent stem cell state. This discovery reflects the peculiarity and exquisiteness of the “unlocking” program design of drug-driven cells “rejuvenating” and provides theoretical guidance for the application of drug-induced cell fate changes.

Due to the absence of introduction of foreign genes, the induction of stem cell pluripotency by the compound of the He Duanqing team is simple, uniform and standardized in the induction process, and will provide a safe and efficient method for the preparation of stem cells for stem cell applications, and has a broad application market. At the same time, it has provided a new direction for drug-induced cell fate transformation, and will greatly promote the development of stem cells and regenerative medicine, serving the medical and health services in China.

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

"The future can be based on the type of stem cells required to design a specific medicine, a purposeful induction of a variety of stem cells." Yan Duanqing said that this is only a beginning, is now further study how to significantly shorten the cell "soaking" time, improve efficiency.

"People's Daily" (12th edition, April 09, 2018)

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