Scientists at the University of Cambridge have carefully cultured human embryonic stem cells for five days to create sex cells.
Studies have shown that the same procedure can transform adult skin tissue into early spermatozoa. Scientists believe that these cells can grow into mature spermatozoa.
The next stage of the study was to inject these blasts into the ovaries of mice and see if they could develop completely.
In the case of positive results, skin cells can be transformed into identically identical sex cells to help adults undergoing IVF therapy.
Suleni, a scientist at the University of Cambridge's Gulden Institute who led the research, said: "We can now take out any kind of embryonic stem cells, and if they are placed in the right environment, they can be manufactured in 5 to 6 days. Out of these primitive cells."
This research is expected to be a milestone in medical development. Researchers have previously used rodent stem cells to make spermatozoa, but it takes effort to use human cells to achieve the same results.
This is the first time scientists have used human cells to make primordial germ cells. The results were published in the journal Cell of the United States on the same day. According to Jacob Hanna, of the Weizmann Institute of Science, who led the study, primordial germ cells appear in the first few weeks of embryonic growth, when embryonic stem cells in fertilized eggs begin to differentiate into the most basic types of cells. . Once such cells are "specialized," they "automatically" transform into sperm cells and egg cells.
Hanna and Azim Shulani of the University of Cambridge in the United Kingdom used induced pluripotent stem cells (iPS cells) in their research. iPS cells are developed by "reprogramming" adult cells, such as skin cells, with similar differentiation potential to embryonic stem cells.
Previously, Japanese scientists have successfully differentiated mouse iPS cells into primordial germ cells, but similar attempts to use human cells have not been successful. Hanna and others found that mouse embryonic cells can be easily maintained in the stem cell state in the laboratory, while human induced pluripotent stem cells tend to differentiate. Therefore, they developed a technique that tuned this differentiation ability to create a novel induced pluripotent stem cell called "primary cells." Hanna said that "initial cells" may be closer to embryonic stem cells in terms of differentiation ability. In their experiments, as many as 40% of human "primary cells" develop into primordial germ cells. In addition, the new study also found that humans and mice have some differences in the differentiation from iPS cells into primordial germ cells. For example, in humans, this differentiation process is a gene called Sox17, and this gene in mice. There is no similar effect.
Hanna stressed that making human primordial germ cells is only the first step in the direction of artificially making sperm and eggs. He believes that this outcome will eventually help some infertile women to become pregnant.
A study published online December 24 in "Cells" showed that scientists not only induced skin cells completely into inducible stem cells (iPS) in vitro, but also differentiated them into human primordial germ cells (hPGCLC, sperm and egg cells). ), the key gene of hPGCLC, the SOX17 gene and the marker substance, CD38 glycoprotein, were also found in vitro.
Israeli and British scientists cultivate human eggs and sperm, and the material comes from a human skin cell. The success of this research will take a step forward in the treatment of infertility, and of course there will be huge controversy and safety review. The study, published online December 24 in "The Cell," scientists first induced skin cells into induced stem cells (iPS), which can differentiate into any cell, including sperm and eggs.
Scientists have first cultivated human sperm and egg cells. Since October 2012, Kyoto University molecular biologist Katsuhiko Hayashi and stem cell scientist Mitinori Saitou have received germplasm cells in vitro, and they have received many emails from couples. Most of these couples are in middle age and are still anxious for one thing: to have a child. One of the British women who had been menopaused was willing to come to his laboratory in Kyoto University for help. She wrote: "This is my only wish."
Looking back at the 2012 paper, the researchers thought that only developmental biologists would be interested in his experimental results. Under in vitro conditions, mouse skin cells are used to create primordial germ cells (PGCs) that can develop into sperm and eggs. To prove that the primordial germ cells cultured in these laboratories are similar to the naturally occurring primordial germ cells, the researchers used them to generate eggs, which in turn created mouse life.
Professor Hayashi said at the time that the life of the created mouse was only a "by-product" of his research, and his research would mean more - using the skin cells of infertile women to provide fertilized egg cells. At the same time, he also suggested that male skin cells can also be used to create eggs. Similarly, female skin cells can also produce sperm. (In fact, after the results of the study were published, many gays sent emails to Hayashi for more information.)
This kind of cell originates from the process of embryonic development, and the individual can produce sperm cells and egg cells after adulthood.
Past human cell culture in vitro attempts: very low success rate
Stem cytologist Professor Saitou uses animal skin cells to induce stem cells, and embryonic stem cells can do the same. Although his cells could not continue to develop, Saito found that if these cells were transplanted into the mouse testis, the cells could differentiate and mature and produce functional sperm. If the cells were transplanted into the mouse ovary, the cells would be transplanted into the mouse ovary. It can differentiate into mature and produce functional eggs, which can be fertilized in the body. The same attempts at human cells have also been partially successful, and germ cells can be cultured in vitro, but the success rate is very low and more research is difficult.
The first experimental principle of fully in vitro culture of mature sperm and egg cells
The study, conducted by the Azim Surani team at the University of Cambridge in the United Kingdom and the Jacob Hanna team at the Weizmann Institute of Science in Israel, pioneered the complete in vitro culture of mature sperm and egg cells.
The key to the success of biologists is to find the right starting point. A major obstacle to the culture of human cells in vitro is that mice and human embryonic stem cells are fundamentally different. Mouse embryonic stem cells are "naive" - ​​easily induced to differentiate into any path; while human stem cells are "mature" and their differentiation The way can not adapt to all the ways. Hanna and his team then established a way to down-regulate the differential genetic signaling pathway, thereby constructing a new type of iPS cells, which they named "na?ve cells." These primitive cells appear to make iPS cells more rejuvenated, closer to the original embryonic state that can truly differentiate into all cell types. Since these primordial cells are more similar to their mouse counterparts, Hanna and the team believe they can be induced to differentiate into primordial germ cells.
Professor Hanna and his collaborators recognized this in a paper last year, and they wrote in the paper that the above difficulties can be overcome by transforming cells.
As stated in their published paper, Primordial germ cells (PGCs) can differentiate into spermatogonia and differentiate into oogonia cells before they enter the genital warts. This differentiation is caused by Determined by the combination of different genital ridge cells. This time, their research constructed an easy-to-manage experimental model, using embryonic stem cells into human primordial germ cells (PGCs), hPGCL-like cells, and found that SOX17 is the key to cultured mature sperm and egg cells in vitro. The gene, CD38 glycoprotein, is a marker added to the surface of human primordial germ cells (hPGCLC).
By adding a red-emitting fluorescent marker (CD38 glycoprotein) to a portion of the primordial germ cell, the researchers can accurately estimate the number of reprogrammed primordial germ cells, and the results show very high efficiency – up to 40 % of the cells become primordial germ cells; this amount enables simple analysis.
Using human skin cells to create germ cells
The scientists also said that primordial germ cells are only the first step in building human sperm and eggs. In the laboratory, a series of events can be completed, and the adult cells are faced with many obstacles before they pass through the embryonic stem cell cycle and become sperm or eggs. For example, at some point in the process, these cells must learn a stunt: divide their DNA into two halves before they become viable germ cells.
From the pictures provided by the author's article, it can be seen that the human gene network is completely different from the gene network previously identified in mice, which may have a significant impact on the future research of primordial germ cells and other early embryonic cells.
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