Fix your eye stem cells with a lot of skill

"The black in front of you is not black. What white is you talking about? If I can see it, life may be completely different..." A "You are my Eye" can often sing and cry in all kinds of variety shows. . According to statistics, 90% of the information received by humans comes from vision, which is one of the reasons why people can best feel helplessness for the blind.

"China has more than 8 million blind people, and one-third are related to retinal degenerative diseases. People with retinitis pigmentosa are blind at the age of 30. They are invisible when they are at their best, and they urgently need treatment." September 19 On the 20th, the Xiangshan Science Conference on the theme of “Regeneration and Personalized Treatment Based on Stem Cell and Genomics” was held. Professor Yin Zhengqin from the First Affiliated Hospital of the Army Military Medical University from the doctor’s point of view, looking for the most suitable It is imperative to enter the clinical treatment more easily.

Stem cell therapy has many advantages in ophthalmic diseases

"This is before treatment, this is a week after transplanting stem cells, this is..." Yin Zhengqin displayed a large number of clinical treatment-related pictures, she said, this is the biggest advantage of ophthalmology research, can clearly see the changes in the lesions And the effect of diagnosis and treatment.

"Ophthalmology does have an advantage. The structure of the retina is very clear. From the choroid to the neurons, each layer has specific stem cell differentiation, and each layer is a different cell type." Fan Guoping, a professor at the University of California, Los Angeles, said. In the blinding of gene mutations, most of the causes are caused by single gene mutations.

That is to say, the eyes are “transparent” in terms of organ structure and pathogenic mechanism. Scientists do not need to “blind people to explore the road” to guess what happens to the eye during the treatment process. The observation methods and the problem-oriented are “clear and pure”. . Fan Guoping said that this is why he has done stem cells for more than 20 years and eventually transferred to ophthalmology research.

Another great advantage is that some part of it has the ability to accept allogeneic stem cells, which Fan Guoping calls “relative immune immunity”. The immune response is not expected to be seen in stem cell transplantation. The body will think that this is "not me" and "strive up and resist", manifesting as symptoms such as edema and suppuration. The immunization exemption has great hope for the transplantation of allogeneic cells.

In addition, the repair work requires very little for therapeutic stem cells. For example, Fan Guoping said that the macular area is basically hundreds of thousands of cells, and most immunotherapy is on the order of billions of cells.

"These advantages make the field of ophthalmology very likely to be a breakthrough in gene therapy and cell therapy," said Fan Guoping.

Lonely "seed" is difficult to survive in a strange environment

Stem cells are considered to be a "seed" that can sprout and grow, but it is often overlooked that "seeds" must also survive in suitable soils.

“Difficult to survive” is an important issue that Liu Yuzhi, a professor at Zhongshan Center of Ophthalmology at Sun Yat-Sen University, has paid close attention to in clinical practice. "Exogenous stem cells enter the body, and in fact they are in an unfamiliar environment. It is difficult to survive without water and soil."

In the clinical application of stem cells, hematopoietic stem cells have the most successful experience, an important reason is that the stem cell environment has not changed.

"The situation of solid organs will not be so smooth. Animal experiments show that exogenous stem cells are transferred into the body by means of vascular injection, local injection of lesions and patch grafting. The cell survival rate is very low and the integration rate is lower. Liu Yizhi said that due to immune rejection and difficulty in establishing neural connections, some effective stem cell transplantation methods will soon fail; and a large number of experiments will fail because the access of foreign stem cells is difficult to “go in the country”, for example, Clinical trials use stem cells to form a myocardial cell membrane, but after implantation, it is impossible to "think about it at one place", and there are problems such as abnormal myocardial pacing and abnormal rhythm, which is difficult to enter the clinic.

From the accumulation of these research phenomena, Liu Yuzhi realized that it is difficult to replace the original organs with "other stoves" in the solid organs. "We also explore the injection of exogenous stem cells into the lens, hoping to grow a new lens, but see abnormal differentiation, lens opacity."

Large incision damage, it is better to leave the "fire"

"The regenerative capacity of lower animal organs has inspired us." Liu said that in fact, part of the adult tissue retains the reproductive capacity of the embryonic period, such as the skin.

Ophthalmologists often find tissue with a certain degree of transparency around the lens after cataract surgery in infants and young children. These unformed lenses indicate their regenerative potential. The question is, what kind of cells have hidden potential? Can you stimulate it and how to stimulate it?

After the marker localization study, Liu Yizhi's team found that the potential cells were epithelial cells in the equator of the lens.

"The damage caused by cataract surgery just lost a lot of lens epithelial stem cells, so it is difficult to regenerate a complete and transparent lens," Liu said. A 6 mm (mm) diameter incision was previously made to avoid cataracts and to sacrifice regenerative "fire."

After finding the crux, Liu Yuzhi team established a new method to reduce the surgical incision to one-sixth of the conventional procedure and guide the incision from the central axis of the visual axis to the edge of the capsule so that the new lens covers the central area of ​​the field of view. Clinical studies have shown that after the new method is performed, the child has a clear visual axis and a clear fundus. At 6 months after surgery, a clear lens was regenerated in situ.

Without ethical controversy, no immune rejection, tissue-specificity, in-situ ordering, and easy integration, in situ regeneration of the lens is considered to be one of the best achievements of regenerative medicine to date due to its significant therapeutic advantages.

Create a "燎原" environment for the "Fire of the Stars"

The success of in situ regeneration of the lens is difficult to replicate directly by other organs.

If the lesions of other organs of the body are understood as the "sweeping" of the enemy's siege in the body, the weak force left by the "sweeping" may be unable to "re-ignite".

The "star fire" is going to be a prairie, and the researchers have done a lot of research. Entering "reinforcement" is one of the methods. "Research shows that exogenous stem cells can promote the growth of endogenous stem cells." Liu Yizhi explained that both the heart disease and the nervous system diseases have found that the original cell pool proliferates to produce new cells and new blood vessels and neural networks.

Liu Yuzhi believes that the possible mechanisms of exogenous treatment to promote endogenous cell regeneration include mimicking cell stress, promoting cell material exchange and exosomal release. Substance exchange is also one of the important mechanisms for exogenous treatment to promote endogenous cell regeneration.

Exogenous cells may not turn themselves into solid tissues, but urge the “indigenous” to grow by secreting substances that stimulate endogenous cells. This is like sending troops, intelligence, etc. without sending troops directly into the battle.

It is better to find "effective elements" through basic research. The former will encounter difficulties in survival, rejection, and difficulty in establishing connections in clinical treatment. The latter not only avoids the previous problems, but also forms standards. , safety effectiveness evaluation, quality control and other aspects are easier to operate.

It is also an effective way to create a micro-environment and help endogenous stem cells to “slow and nourish”. The research by Liu Yuzhi's team showed that for the reconstruction of transparent cornea, only the limbal stem cells were difficult to repair before, and the transplantation of autologous adult stem cells and basal stem cells could be reconstructed. Can be understood as a "moving" type of stem cell transplantation.

In addition, the application of novel biomaterials is another effective way to promote endogenous regeneration. "These materials are mostly biodegradable biomaterials, and the structure fully mimics the cell scaffolds in tissues and organs, providing physical support for the endogenous regeneration of cells," said Liu Yuzhi.

Transplanting stem cells directly into the injury site, although it seems to be “short and fast”, may ignore the complexity of stem cells because of simplicity and “recklessness”. In the process of stem cell biotechnology moving toward clinical treatment, more wisdom is urgently needed. And strategy, to avoid its shortcomings such as heterogeneity, lack of stability, and more to play the "smartness" of stem cells.


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