"Sure enough, it worked. The rat's spinal cord injury recovered."
Chen Yiqing looked at the squeaking and energetic rats in the cage, his eyes were a little dazed, and he murmured to himself.
A week ago, he received a neural stem cell transplant from Ding Mian.
In fact, this thing was not as easy to use as he imagined. Ding Mian also spent a lot of effort to cultivate a jar of rat neural stem cell suspension and handed it over.
The next preclinical animal study is very simple.
There are no other animals in Chen Yiqing's laboratory. There are rats with all kinds of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, ALS, etc.
There are even many mice with broken legs, crooked necks, and various high paraplegias.
So he quickly gathered 30 very fresh rats with spinal cord injuries, divided into control group, injury group and transplantation group, with 10 rats in each group.
At first, the rats screamed, their limbs were weak, and they could only lie on the bottom of the cage, looking quite miserable.
Subsequently, the experimenter waved the thick needle in his hand and injected the neural stem cell suspension one by one into the injured spinal cord of the rats in the transplant group.
As for the rats in the injury group, they also received in-depth greetings from the needle, but they were injected with the same amount of normal saline.
Soon, things changed significantly.
The rats in the injury group and control group were still lethargic, but the damaged spinal nerves began to repair spontaneously.
Purely natural, without artificial intervention, but it is slow and the effect is not satisfactory.
There are actually a small number of endogenous neural stem cells in the spinal cord of animals. They are silent at ordinary times, as if they do not exist. However, once the spinal cord is damaged, they can be quickly triggered.
These neural stem cells in the spinal cord continue to proliferate, migrate all the way to the lesion site, and then differentiate into a large number of astrocytes and a small number of oligodendrocytes, thus forming glial scars.
During the period of spinal cord injury, these neural stem cells also regulate the inflammatory and immune microenvironment and secrete neurotrophic molecules such as growth factors.
In short, we are investing both money and efforts to repair damaged nerves and create a nutritious convalescent environment.
It looks pretty good. If it can keep up, there will be nothing wrong with humans.
Unfortunately, these endogenous neural stem cells are very limited in number.
If humans do not intervene, these pitiful neural stem cells will basically be unable to do much work and will be exhausted.
Therefore, according to the basic laws of the development of nature, the iron-blooded principles of biological evolution over hundreds of millions of years - just make do with it.
These rare neural stem cells, as expected, differentiated into glial cells, forming a large number of scars, causing holes and breaks in the spinal cord tracts.
This may be what nature thinks. If you fall down from a high place, your neck will be crooked.
The first reaction must be to stop the bleeding, let the bones and muscles grow back, and get out of danger as soon as possible.
As for the nerves being severed and unable to be reconnected, and the spinal cord being covered with scars, that doesn't matter.
Not every animal wants to die like this and will break its neck.
What? You said that some animals really had their spinal cords broken and their limbs became paralyzed.
Deserve it!
Eliminate immediately!
Basically, most living things evolve according to such a set of rules.
Therefore, making do with what is available has become the first principle of biological evolution.
As long as you can survive, it doesn't matter.
Anyway, those who don’t adapt will be eliminated.
As for optimization and reorganization, that is impossible, not even in this life.
Therefore, when humans began to study biology, seeing the traces of sewing on these chromosomes and embryos was exactly the same as the mood of programmers when they saw the shit mountain code.
But I had no choice but to hold my nose, hold a microscope and a needle, poke here and look there to see if I could fix the functional failure.
Right now, that's what Chen Yiqing is doing.
The neural stem cells in the rat's body cannot be allowed to let themselves go and grow wantonly, turning into scars of disconnected nerve bundles.
It is necessary to control the differentiation direction of neural stem cells in the spinal cord just like parents interfere with their children's learning.
When a child takes the wrong path, the parents suffer, and their wallets suffer heavy losses.
When cells go the wrong way, patients naturally suffer, but researchers' KPIs also suffer heavy losses.
This also gives the two a strong driving force to wield the whip/needle.
Since neural stem cells are allowed to develop on their own, they can only differentiate into astrocytes instead of neurons and oligodendrocytes, which greatly limits their regenerative effect.
He will culture the neural stem cells in vitro, and then add immune T cells and various cytokines to control its differentiation direction.
Not only does it accurately differentiate into neuronal cells, it also repairs myelination, supports the growth of axons and blood vessels, and achieves the purpose of repairing spinal cord damage.
A large number of differentiated neuronal cells can be used as a source of cells for damage repair, replenishing damaged nerve cells, and also greatly reducing the formation of glial scars.
Of course, neural stem cells also secrete various neurotrophic factors during the differentiation process.
Growth factors, for example, can support the growth of motor and sensory axons.
Vascular endothelial growth factor can promote the growth of damaged blood vessels.
Neural stem cells that grow wildly will only turn into clumps of glial cells, just like ice floes on the river, with no normal connection function at all.
Over time, when the river dries up, a fractured riverbed will be exposed, completely blocking signal transmission in the nervous system.
Under human control, neuron cells grow axons, just like the steel bars of a bridge, connecting the two ends of the river bank, and the surrounding area is filled with glial cells. This is normal and healthy nerve cell tissue.
The rats in the transplant group were in sharp contrast to the rats in the injury group and the control group who were left to their own devices.
The neural stem cell suspension injected into the body first effectively fills the damaged lesions.
It then differentiates into a large number of neuronal cells and glial cells, replacing the missing cellular components.
These neuronal cells, including a variety of intermediate motor neurons and sensory neurons, send out axons into normal spinal cord tissue and establish synaptic connections with downstream neurons.
The axons continued to grow, entering the brainstem cranially and extending caudally beyond 14 spinal cord segments to the tail end of the rat's body.
At the same time, neural stem cells secrete a large amount of nutrient molecules, which greatly promotes the regeneration of descending motor axons (such as CST and 5-HT axons) and ascending sensory axons of the spinal cord.
The regenerated axons establish functional synaptic connections with newly differentiated neurons, thereby reestablishing the continuity of spinal nerve signaling pathways.
In addition to neurons, neural stem cells can also differentiate into non-neural cells, such as oligodendrocytes, which participate in the formation of myelin and maintain the stability of nerve conduction.
In addition, there is a nutritional environment created by neural stem cells.
A large number of corticospinal tracts also spontaneously enter the injury focus and gather in clusters, forming a spatial distribution similar to the layered structure of normal spinal cord gray matter.
In these spaces, regenerated neurons and densely growing axons are connected layer by layer and spread throughout, establishing a neural network that spreads around.
At this point, the nerve damage to the spinal cord has been completely filled and repaired.
This series of experiments is enough to prove that neural stem cell transplantation can repair spinal cord damage to the greatest extent and bring it close to a physiologically healthy state.
Chen Yiqing was not as cold-blooded as Ding Mian. After observing signs of recovery from spinal cord injury, he did not immediately terminate the experiment and wipe out the lives of 30 rats, but continued the experiment.
In the past, after neural stem cells were transplanted into animals, it took a long time to differentiate into mature cells, which lasted up to 1 year.
But accelerated by additional growth factors, the number and distance of axon regeneration reached a peak in the rat spinal cord 1 month after stem cell transplantation.
By three months after transplantation, the number of axons had almost halved.
"Sure enough, the differentiation process of transplanted neural stem cells is very similar to the development of the mammalian nervous system."
During these three months, Chen Yiqing stayed in the laboratory almost without sleep or food, and plunged into the arms of the rats.
Even though he was prepared for the effect of stem cell transplantation in repairing the spinal cord, when this discovery appeared before his eyes, his pupils still trembled.
"It can be speculated that the process of axon regeneration also undergoes functional selection and elimination."
"The nervous system performs delicate pruning on the large number of regenerated axons, removing unnecessary axons, just like a gardener pruning the branches, leaves and weeds of trees."
"Such a regeneration and remodeling mechanism lays the foundation for establishing functional neural circuits and reducing side effects after neural stem cell transplantation."
Chen Yiqing stood up from the microscope and paced back and forth in the laboratory, still unable to restrain his excitement.
The corners of his brows and eyes couldn't help but exude joy.
"Great, I finally understand the entire process of neural stem cell transplantation."
"I can't wait to use it on patients."
He was so excited, but he still did not lose his mind. Instead, he immediately thought of some key information about stem cell clinical experiments.
"Stem cell therapy is no longer uncommon. There are related products on the market at home and abroad, and the relevant review regulations are also relatively complete."
"So in terms of safety, there is not a big problem. There are a lot of clinical studies to support it."
"It shouldn't be too difficult to pass the review. I just need to design a rigorous experimental plan based on the product characteristics."
"After years of research on ALS, I have accumulated a lot of cases. Once the review is approved, clinical trials should be able to start immediately."
Thinking of this, he was eager to try it, and at the same time he was a little emotional.
"It took so long that only after the breakthrough of stem cell therapy could we find the glimmer of hope for treating ALS."
"It's really a trick of fate. I wish I had known it earlier. I will definitely keep an eye on Ding Mian every day and complete the research in this area as soon as possible."
Chen Yiqing thought of doing it and took action immediately.
Due to the particularity of stem cell research, which involves a large number of ethical considerations, domestic regulation is very strict.
According to the "double filing" requirement, not only must it apply for approval from the Food and Drug Administration, but it must also jointly file with the National Health Commission.
At the same time, the qualification review of stem cell clinical research institutions is also very demanding.
It can only be a tertiary-level hospital, and it must undertake major provincial scientific research projects. The most rare thing is that the project leader must have a senior professional title.
This requirement is not unusually high. Ordinary CRO outsourcing medical institutions are simply not qualified to conduct clinical research in this area.
In short, it reflects the high, precise and cutting-edge scientific research requirements in all aspects.
Fortunately, most of Sanqing's cooperative scientific research institutions are tertiary hospitals, and many of them can still meet the standards.
Especially at the Kunming First People's Hospital, ever since Jian Lianyun was promoted to director of neurosurgery with the brain-computer interface, a national key project.
Research in neuroscience between the two parties has become closer than ever.
Chen Yiqing immediately called Jian Lianyun and wanted to file the project with the hospital.
"Director Jian, I, Old Chen, by the way, want to tell you something."
"We have a new stem cell project in our laboratory, mainly for clinical research on ALS."
"Yes, current experiments on rats have confirmed that neural stem cells and immune T cells can repair spinal cord injuries, especially motor nerve injuries, after combined transplantation."
"So I want to start clinical phase I trials as soon as possible. As you know, clinical research on stem cells is quite special..."
"Old Chen, it seems you have a deep love for ALS. Hahaha~"
Jian Jian Yun's crisp voice came over, with a hint of teasing in his excitement.
"It went round and round, experienced so much in the middle, and finally came back to the same place. You really paid too much for ALS."
"Okay, you send me the information, and I will immediately set up an expert group and ethics committee, and then submit the declaration."
"Don't worry, if everything goes well, it will be completed within three days."
She was originally very capable of doing things and her execution ability was outstanding. After becoming the director, she had great power and her style became more vigorous and resolute, which made Chen Yiqing very satisfied.
"Director Jian, just laugh at me. In order to treat ALS, I really put in a lot of effort, and I even made a brain-computer interface in the process, and the effect is actually pretty good."
Chen Yiqing laughed happily: "Now I have finally found a way to treat ALS. It can be said that I have to stay true to my original intention."
"Okay, okay, congratulations, you got what you wanted. I have another surgery later. I'll talk to you after reading the information."
As a department director and an academic leader in the field of neuromedicine in China, Jian Jian Yun is really busy, and when he makes phone calls, he is also very concise, without a word of nonsense.
After all the information that should be exchanged was exchanged, he immediately hung up the phone and rushed to the next target.
Chen Yiqing has worked with her for many years and is used to this style.
"The hospital is still busy. Compared with her, we are much more leisurely."
He thought to himself, came to the office, and prepared the filing materials.
(End of chapter)
