Chinese scholars have used gene editing techniques for the first time to gain genetically enhanced "super" stem cells
"Wolverine" and "spider-man," these Hollywood blockbusters are famous for their superheroes.
But in real life, genetically modified reproductive cells to create these genetically enhanced "superhuman beings" are prohibited by ethics.
And in ethical licensed stem cells, Chinese scientists have genetically engineered the first genetically enhanced "super" stem cells.
Such stem cells could be used in treating human diseases.
On July 7th,the Cell Research published online journals in the institute of biophysics, Chinese academy of sciences Liu Guanghui team, the team and of cas animal Research institute of Beijing university Shang Fu pay for QuJing joint Research team, the gene editing technique is first applied in the genetic enhancement of Stem cells, which announced the first Genetically Enhanced on international Stem cells, GES cells.
As you know, stem cells are a class of self-replicating cells that can be differentiated into many functional cells under certain conditions.
So what are these new stem cells?
In an interview with surging news (www.thepaper.cn), Liu Guanghui said: "' genetic 'means that the genetic code of the stem cell is changed, we use gene editing techniques to rewrite a single base in the human genome. The changes in the genome in the process of stem cells, can be stably transmitted to daughter cells."
"Enhanced" means that after this tiny genetic code replacement, the stem cells are "old" to be slower, which can survive longer in the patient's body and produce better regenerative treatment.
In addition, the stem cells can also protect against the anti-cancer gene, reducing the risk of converting to cancer cells.
It is because of the same resistance to cell aging and cancer that is known as "genetic enhancement" stem cells.
Institute of zoology, Chinese academy of sciences state key laboratory of stem cells and reproductive biology researcher li wei, who was not involved in the study, he told the surging news commented: "this finding transformation of ectomesenchymal stem cells for clinical treatment is of great value, but also well confirmed the use of gene editing techniques can promote the application of stem cells in regenerative medicine, for stem cell research provides a new method is worthy of learning."
This "super" stem cell is to solve two of the most difficult problems in stem cell therapy - the effectiveness and safety of the treatment.
Liu guanghui's team and its collaborators have only changed one base in the human genome through gene editing techniques. accomplish a great task with little effort by clever maneuvers to solve these two puzzles.
The key change to "accomplish a great task with little effort by clever maneuvers" revolves around the transcription factor called NRF2.
A transcription factor is a protein that helps the DNA of a genetic material to be transcribed into RNA.
In the work of liu guanghui and his collaborators, they tried to find key factors related to stem cell aging in the way they were screened by drugs.
In the process, they found that screening for compounds that could slow the aging of human mesenchymal stem cells had one common trait - both activating NRF2, an antioxidant transcription factor.
Thus, liu's team speculated that enhancing NRF2 activity at the genetic level might slow the aging of human stem cells.
In previous studies, researchers have known that the NRF2 inhibitory protein, known as KEAP1 in cells, binds and degrades NRF2 so that it doesn't function.
At the same time, researchers have known that on the surface of NRF2's contact with the inhibitory protein, there is a key amino acid that binds NRF2 to the inhibitory protein.
So, if this key amino acid is replaced, does NRF2 get rid of the inhibiting protein and better function and protect the cell?
Therefore, in order to prove this conjecture, in human embryonic stem cells, Liu Guanghui teams use third-generation adenovirus vector HDAdV mediated gene editing techniques, replace the NRF2 gene encoding a base (A245G).
After replacement, NRF2 sure enough to break out of the "control" of inhibiting protein into the nucleus in great quantities, to activate a series of antioxidant and cellular protection of gene expression, made the stem cells have a longer "life".
Then, liu's team and its collaborators tested the effect of the artificially modified stem cells in the body.
It is worth mentioning that in stem cell therapy, because embryonic stem cells could form a benign teratoma and cannot be used directly, composed of embryonic stem cells, directional differentiation of mesenchymal stem cells are better between the treatment of materials.
Therefore, liu guanghui team differentiated from the modified human embryonic stem cells into mesenchymal stem cells and carried out experiments on mice.
In the experiment, the large blood vessels in the legs of the mice were ligated with ischemic injury.
The researchers then injected stem cells into the legs of the mice, helping the mice to regenerate new blood vessel cells and reconstructing the vascular system.
Results show that compared with no stem cells that genetically editor after genetic enhancement of mesenchymal stem cells can be significantly between return leg blood circulation, has better ability of regeneration.
Good effect, but are there any security risks?
This is a scientific problem that researchers cannot get around.
Then, liu guanghui team and its collaborators conducted a security assessment.
To their surprise, the genetically engineered mesenchymal stem cells, despite their stronger self-renewal abilities, did not form tumors in mice.
Even in the case of many oncogenes, it maintains a high degree of genomic stability and has a strong "resistance" to cancer-induced cell malignancy.
More thought is, to the question of embryonic stem cells will appear teratoma, they found that compared with ordinary embryonic stem cells that genetically editor of the ability of embryonic stem cells produce teratoma is greatly weakened, further increase the chip on the treatment of "security".
To make a long story short，By replacing one of the bases of NRF2 encoding genes, stem cells have acquired a stronger regenerative repair capability and significantly reduced security risks.
Such genetic enhanced "super" stem cells have the advantage of being standardized and scalable, and can be applied to many therapeutic scenarios in the future.
Now researchers have patented the technology.
But liu also cautioned against the paper, speculating that the use of such cells should be limited.
Currently, they have demonstrated that this genetic enhancement strategy applies to human mesenchymal stem cells and vascular endothelial cells, but has not yet been tested for its efficacy and safety in all cell types.
For example, the self-renewal of neural stem cells requires reactive oxygen, and the anti-oxidative transcription factor NRF2 enhanced, will the neural stem cells benefit?
This is still a question mark.
"Any type of cell in our body, in theory, has a unique internal and external environment that they love."
According to liu, genetic enhancement strategies such as neural stem cells can be designed to be personalized.
Shanghai life science research institute, Chinese academy of sciences researcher at the institute of nutrition science Ding Qiurong was not involved in the study, she to surging news, said Liu Guanghui and others put forward the strategies of genetic enhancement on stem cell has the very broad application prospects.
"(this) can be widely used in regenerative medicine, to strengthen the regulation of stem cell transplants, make it better as well as tissue engineering and technology integration, in vitro cell mass preparation, class organ function module build, directional differentiation, transplantation into the class body organs, blood vessels and nerve process, the body in the process of the micro environmental improvement and tissue repair more guidance and control, promoting the transformation of its clinical."
"Said ding.
"Of course, changes in the genetic code need to be very deliberate, based on the full understanding of the post-modified cell characteristics and the full assessment of the safety of the body."
"Added ding.