Can damaged organs be repaired? "Human body 4S shop" is becoming a reality!

At the 37th "Healthy Line of Defense" lecture of "Science Popularization China - I am a Scientist", Dai Jianwu, researcher at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, director of the Center for Regenerative Medicine Research, director of the Chinese Society of Biomaterials, and secretary-general of the Stem Cell Branch of the Chinese Society of Cell Biology, gave a speech entitled "Human Tissue and Organ Repair, Regenerative Medicine Moves Beyond Science Fiction".

The following is the transcript of Dai Jianwu’s speech:

2022.4.17 Beijing

Hello everyone, my name is Dai Jianwu, I am from the Chinese Academy of Sciences, and I am engaged in regenerative medicine research.

Just now, Dr. Tao Yong told the story of ophthalmology. We know that there is a surgery in ophthalmology called corneal transplantation, which can restore the sight of many people who are blind due to corneal diseases. In fact, with the development of modern medicine, organ transplantation is no longer limited to one type, but more than ten types - including the common major organs of our heart, liver, lungs and kidneys - can be transplanted.

Organ transplantation is often the last resort for treating organ failure, but there are still many obstacles. For example, organ transplant patients have to take anti-rejection drugs for their entire lives, which also suppresses their own immune system, so there are many side effects. Of course, the biggest obstacle comes from the supply and demand relationship. There are hundreds of thousands or even millions of people waiting for organ transplantation in my country, but only about 1% of them can wait for organ supply.

Whether it is mythology in the past or science fiction today, whether organs can regenerate is a theme. Humans dream of organ regeneration, but unfortunately it is difficult, because from an evolutionary perspective, human organs have evolved for tens of thousands of years and are highly complex, and have lost a lot of regenerative abilities; on the contrary, if you cut off the limbs of lower organisms like the salamander in the video, it will definitely grow an identical one within two months.

Over the years, people have placed their hopes for organ regeneration on a new discipline called regenerative medicine, which is the story I will tell you today. You may have some understanding of regenerative medicine because many people have heard of stem cells, but this is actually a one-sided understanding of regenerative medicine because stem cells are an important part of regenerative medicine, but not all of it.

I personally believe that regenerative medicine is a systematic project that requires scaffold materials to determine the location of cells and regulate cell functions. In addition, various regenerative factors are needed to help cells survive, differentiate and grow. Stem cells are just the seeds of a cell. Regenerative medicine is actually like building a house. If you only have bricks (stem cells), you certainly can't build a building, because you need a strong steel scaffold (biological scaffold material) to support the entire house; if you have bricks and steel bars, you can build the house, but it still has no function, and you need water, heating, electricity (regenerative factors), etc. Therefore, my own understanding of regenerative medicine is based on biological scaffold materials, combined with stem cells and various regenerative factors, to repair, rebuild and manufacture the tissues and organs that the human body wants.

I returned to China in 2001, and the first thing I did was to establish a regenerative medicine laboratory. After establishing the laboratory, we first had to determine its scientific problems. We took the most difficult problem in regenerative medicine, spinal cord injury, as the direction of the laboratory. Many people advised me that Professor Dai should consider easier problems, which would be easier to produce results. But when you see patients with spinal cord injuries, you feel that these problems must be solved by someone.

In my country, there are about 100,000 to 140,000 spinal cord injuries each year due to accidents, work-related injuries or diseases. There are more than two million spinal cord injury patients living in our country, most of whom are young individuals. Although their survival ability has not changed much, the heavy economic burden and care work will drag down their families.

The spinal cord is a nerve pathway in our spine, just like a cable, through which the brain's command action signals are transmitted to the limbs, and through which the limbs' sensations are transmitted to the brain. However, if any part of the cervical, thoracic, or lumbar segments (such as the red dot in the video) is damaged, the signal pathway will be terminated, and the lower part of the damaged site will have no sensation, which we call paraplegia.

Why is it so difficult to repair spinal cord injuries? Because theoretically, spinal cord tissue cannot regenerate at all. It is not like what we often hear: "It takes a hundred days to heal a broken bone." Bone and skin injuries have a self-healing process. Once damaged, a large number of stem cells or growth factors will go to the injured area to help regenerate. But spinal cord injuries are different, including brain injuries. The reason why the central nervous system cannot regenerate is from a protective perspective. Once damaged, it will form a large number of glial scars to prevent further damage and hinder regeneration. Therefore, in the process of spinal cord injury and regeneration research, we mainly think about how to rebuild a regenerative microenvironment.

The term "microenvironment" sounds very abstract. You may have heard more about the macroscopic business environment, living environment, etc. In fact, if we take out any tissue as big as a sesame seed or a millet grain and put it under a microscope, it is probably the structure on the left side of the above picture, with many scaffolds, extracellular matrix and structural proteins to support the position and existence of various cells; in addition, there are many regeneration factors and signal molecules, which support the generation and differentiation of cells through the concentration gradient formed by the scaffold material. To change it from a microenvironment that inhibits regeneration to a microenvironment that promotes regeneration, it is necessary to use biomaterials to regulate cells and the distribution of growth factors, which requires core technology.

In the past twenty years, we have developed roughly two key technologies.

The first is to modify biomaterials so that they can regulate the spatial distribution of various growth factors in the liquid, including the ability to form gradients. So far, this should be the most cutting-edge technology in the field. Similarly, we can position cells in a liquid environment, regulate cells and growth factors through the role of scaffolds, and rebuild the regenerative microenvironment. Based on this theory, we designed a scaffold material product for spinal cord tissue regeneration, which is also the first such product in the world.

NeuroRegen® Collagen Scaffold for Nerve Regeneration

As you can see from the photo, the scaffold is made up of collagen fibers arranged longitudinally, which actually guide the nerves to grow in this direction.

Two months

Four months

So after implanting this product into an animal with complete spinal cord injury, you can see that the animal actually had no functional recovery after two months, but after three or four months, the dog could slowly stand up and walk on its own. This is the first time we have seen a product that can truly guide spinal cord tissue regeneration.

As a product, what is its mechanism of action? Traditionally, everyone believes that nerve regeneration will grow by one millimeter or a few tenths of a millimeter per week or day. In fact, this is for peripheral nerves that can regenerate. After a period of time after injury, the function will slowly recover, but the central nervous system cannot do this, so we can only propose our own theory based on the data accumulated over the past 20 years.

We found that spinal cord injury can activate many cells, for example, glial cells can differentiate into Nestin-positive neural stem cells. At this time, if they are guided to differentiate into blue neurons, these neurons can form connections with nerves in normal tissues. Just like when we watch war movies, the telephone line is cut off and cannot be connected, so the soldiers simply use their hands to connect it. I think the mechanism of spinal cord injury regeneration that we have completed now is basically the same, connecting the two broken ends of the nerves at the injured site, allowing neurotransmitters to spread, and thus restoring function.

We started preparing for clinical trials for this product in 2014, and the first patient was officially enrolled on January 16, 2015. So far, it has been seven years, and a total of more than 100 patients have undergone clinical trials. Last year, we just published a paper on 51 patients with a five-year follow-up, proving that the product is safe and effective for more than 50% of patients, especially acute injuries, and 40% of patients can recover their motor function.

There was a young girl in the case who cooperated very well with rehabilitation. She was the only one among more than 100 patients who could walk independently. She gave us a lot of hope, indicating that patients with spinal cord injuries do not need to sit in wheelchairs for their whole lives. They will stand up and walk one day.

In this picture, I review some of the milestone work in our laboratory over the past 20 years in spinal cord injury research; but there are many things that cannot be written in it because they are all failed work.

At this point, I have two thoughts to share with you:

First, scientists must be able to endure loneliness and stick to a goal. We have been working on spinal cord injury for 20 years, and I still have 20 years to work on spinal cord injury. We want to take the treatment of spinal cord injury to a higher level. In fact, it is very important for scientists to focus on a scientific problem. You may envy the Japanese who win the Nobel Prize every October, but if you study these people, you will find that they focus on a scientific problem throughout their lives, unlike some scientists who may chase this hot spot and that hot spot and finally achieve nothing.

The second is that scientists should not be afraid of difficulties. We have chosen the most difficult scientific problem, which has allowed us to push the core technology of regenerative medicine to the extreme. Conversely, when we face other tissues and organs that are easy to regenerate, it will be easier to achieve results.

Over the past decade, we have also carried out clinical research on other regenerative medicine, including endometrial damage.

Every year, there are more than 10 million artificial abortions in our country, which can cause a lot of damage and scarring of the endometrium, and even infertility. We worked with Hu Yali's team at Nanjing Drum Tower Hospital to design a collagen membrane to repair the endometrium. Clinical trials began in 2013, and on July 17, 2014, the first baby from the endometrial regeneration clinical study was born. I participated in the delivery in the delivery room and was deeply impressed. So far, this clinical study has produced nearly 100 healthy babies, all through endometrial regeneration.

Another one related to reproduction is premature ovarian failure. Some young people stop menstruating at the age of 19 or 20, and their ovaries are not activated, so there is no question of pregnancy and childbirth. In response to the incurable disease of premature ovarian failure, we worked with Director Sun Haixiang of the Reproductive Center of Nanjing Drum Tower Hospital to design an injectable stent, which is mainly to guide blood circulation around the ovaries and help the development of the ovaries. We found that all 20 patients were able to activate their ovaries, and two of them became pregnant, but one of them was diagnosed with trisomy 21 because of her older age, and the pregnancy could only be terminated. Finally, on January 12, 2018, the first patient in the world who was clinically treated for premature ovarian failure gave birth to the first baby at Nanjing Drum Tower Hospital. This is also a landmark achievement, proving that premature ovarian failure is no longer an incurable disease.

Myocardial regeneration is actually very difficult. You may think that myocardium is a non-regenerative tissue like the spinal cord, but the demand for myocardial regeneration is very high. Half of the deaths in our country and even in the world each year are caused by cardiovascular diseases and tumors. After a myocardial infarction, the myocardium will become fibrotic, forming a barren land, reducing heart function and compensatory hypertrophy. The treatment method is stenting, then bypassing, and finally heart transplantation.

We applied the concept of desert control to myocardial regeneration. If a piece of land is desertified, it will become an oasis if water is introduced. If blood vessels are grown in the necrotic myocardium, can the myocardium be regenerated? So we designed an injectable collagen and found that it can make the myocardium grow again in a pig myocardial infarction model. In March 2016, we organized a clinical study of 60 patients with heart failure. After a year of follow-up, we found that the myocardium of patients with severe heart failure can indeed regenerate. So I think this clinical significance is very great and can bring hope to countless cardiovascular patients, especially myocardial infarction patients. This work was recently published in the clinically famous JAMA magazine.

Finally, we are also concerned about the issue of beauty and vocal cord regeneration. We cooperated with Director Jin Xiaofeng of the Department of Otolaryngology at Peking Union Medical College Hospital. They brought many patients' needs, saying that these patients could not speak clearly or could not speak for some reason. Is there any way to solve this problem? From the perspective of the vocal cord structure, it is a ligament. If the ligament can regenerate, the vocal cord may be able to regenerate. So we designed an injectable collagen scaffold to repair the vocal cords. Since 2016, we have done 20 patients at Union Medical College, and the results show that the efficiency is 100%. Let's listen to an example -

The higher voice is after treatment, and the lower voice is before treatment. The latter patient came to my office specifically with Director Jin to thank us. He said that he had no confidence in speaking before, but now he feels that he speaks louder than the average person, and I am very happy for him.

In fact, there are many areas where vocal cord regeneration can be used. For example, many young people like to sing, but some of them can’t sing high notes. Regenerative medicine can be used to increase the elasticity and width of the vocal cords, which may make the voice louder. So I think it can also beautify the voice.

Having said so much, I actually recalled some dreams. In 2014, I was selected as CCTV's annual science and technology innovation figure for my achievements in endometrial regeneration. At that time, I put forward a fantasy during my speech. I said that people are the same as cars. Cars have 4S stores for regular maintenance, problems can be repaired, and faults can be replaced with parts. I think regenerative medicine also provides a dream for humans, and can also achieve maintenance and repair of the human body, and even replacement of parts. Today, I stand on the stage, and I feel that the dream I brought to everyone is becoming a reality.

Thank you everyone.

Speaker Dai Jianwu: "Human tissue and organ repair, regenerative medicine goes beyond science fiction" | Photo: Vphoto

Source: Science Popularization China-I am a Scientist