June 25, 2014

Immortals patched with heart

One of the leading world biophysicists, Professor Konstantin MIPT Agladze returned home after many years of work in the United States and Japan. Three years ago he received a mega-grants, and now he has his own laboratory in the Physical-Technical Institute, which deals with tissue engineered heart. K.Agladze sure that in the near future, people can live almost forever. Professor told reporters RBC Cyril Alexander Sirotkin and Fedotova about immortality, patches on the heart and Japanese taxi drivers.

Konstantin I., in a recent television interview, you promised to mankind immortality. Tell us more about his research, the patch on the heart and all interests immortality.
For a start, I did not promise, and drew attention as to research in immortality have an indirect relationship. The orbit of my life came in contact with the orbits of the lives of those who are actively working with induced pluripotent cells-. All this noise erupted because these researchers have learned to make artificial human tissue. And they only artificial procedure. In fact - they are natural, because the source of their natural - human fibroblasts. Fibroblasts - connective tissue cells is the most unpretentious fabric, which is in the body. They learned how to reprogram the cells of another type. This was made possible by Shinya Yamanaka (Japanese scientist, Nobel Prize in Physiology or Medicine 2012. - Note. RBC). He gets them from pluripotent cells that can be done by specialized cells.

There is the possibility of radical renewal of tissue. Upgrade Procedure tissues such as heart and liver, will be developed in the coming years.
Why is it important-for example, you are greatly cut hand - remains a scar for life, because the wound is not overgrown muscle tissue and connective tissue disorders. Reprogramming cells enables cells scar translate back - a state specialized normal cells.
Or cirrhosis - is replacement of liver tissue by connective - the so-called granulation, and can not reverse the process. A reprogramming cells enables remove cirrhosis. This is what the Japanese are now working, and I'm sure everything will be done successfully. However, while the methods used are very oncogenic, they can cause tumor growth, it is now a major issue.
And over what you are currently working,
I - biophysicist, my lifelong interest was in the study of complex cellular systems, in particular excitable tissues such as the heart. In Kyoto, we worked in collaboration with molecular biologists. Of induced pluripotent stem cells of interest to me, because they can be a source of human heart cells.
Why is it so important, point is that scientists are conducting experiments on animals as old as there are experimental physiology, molecular biology now much headway on developing animal models of human medicine. But it does not always work. Human cell and cell, say, rats behave differently, different ion channels. Therefore, to test drugs on rat cells is not always possible, because the drugs must be for a person.
Find the opportunity to work on human cells is very important, and will be their source of reprogramming. If you have a line of pluripotent cells, you can get a tissue of the body, which can work. For example, we will make the pieces of heart tissue. This part is only transferred to the Russian soil. This is something that should work directly in the next year or two.
The first goal is close enough: check will act as human medications, antiarrhythmics. Cardiac arrhythmia - this is the beginning of a process that takes the lives of most people. Tachyarrhythmia occurs that develops paroxysmal states, fibrillation of the heart. Next know yourself - in the modern world literally stuck defibrillators. This thing is very important, it is demanded, in many cases, the timely use allows people back to life. But in order to prevent arrhythmias and atrial fibrillation, need effective antiarrhythmics. And they need to develop human tissues.
Comes to interesting things. I saw something in the article that the drug is tested on excised human heart. It shocked me, I began to find out where they took heart. It turns out that when doing transplant old heart to take research - that will have time until it lives. Of course, such experiments are very interesting, but it's unique moments - not quite regular, not predictable. Such work can be done, but very dotted.


As in our experiments, we look the source of arrhythmia-We give a fluorescent label and using highly sensitive cameras see the wave of excitement spread through the cells of the heart. At this point, we can intervene to instill some substance to see how it will affect the wave. If the wave broke and formed a vortex - a precursor of atrial fibrillation, we can understand what to do, so he left. Often these waves are torn because of the interaction with obstacles: the wave goes around them and can not go around, breaks, twisted vortices. We published an article co-authors of such a mechanism for the formation of spiral waves in Science back in 1994., And then in 2007. I confirmed in my work, it really works on the heart. Where such obstacles are taken-If a person had a heart attack, it leaves a scar, and this scar is not going anywhere. When a person dies, and conduct an autopsy, the doctor may say that 25 years ago he had a heart attack, because traces remain forever.
A reprogramming cells enables these scars away. And this is not some bullshit type injection of stem cells, which many states have done in the U.S. is actively engaged in this.
With reprogramming cells became possible to restore them, so they started with a clean slate. But the development of rejuvenation procedures we do not, we are at the level of heart problems biophysics. This is important, what we do, what interests me.
If you do not have animals, where you take heart for experiments-
We are working on the preparations of the heart, because the heart of the whole picture of the excitation is very complicated. Researchers are working, for example, pig heart (it is most similar to human) suspend it, perfused with nutrient solutions ... But since recorded a very complicated picture, it is necessary to simplify the experimental model in order to understand the fundamental mechanisms. This is the normal approach to physics: life is very complicated, so it will divide into simple components. Maximum simplification - to a single cell.
Many Western pharmaceutical companies, which have their own R @ D (research departments. - Note. RBC), work on single cells. They are excitable, they put micropipette spelled activity of the cell under different medications. Thereafter, test drug on animal models - rat or monkey. But monkeys are very expensive, not to mention the ethical issues. A single cell and an ensemble of cells behave differently. You change, for example, the activity of cells and think that they changed its excitability, some ionic currents, but you do not know how this medication changed from cellular communication. Cellular molecular machinery we do not know to the extent to accurately predict all.
We know about as much as the XIV century explorers knew about the world: they already knew the coast of Europe, if that must swim somewhere, probably priplyvesh to India, but did not even know that there is America, that the Earth is round. We are now in the same way. This does not mean that we will never be known, but it will take decades to come, and medication is needed now.
Therefore, to see how the medication works, you need a heart medication: cut a piece of heart and see how it works. So worked classical experimental electrophysiology. However, when cut, produces a lot of damage, because there are edge, damaged cells, which began necrosis. A cultured tissue just effectively fills the gap between research and the behavior of an individual cell research on the whole animal. Tissue culture, we do not come up, we do not come up to pour her some medicine. But we did a lot themselves. For example, we learned how to create a structured culture. We first simplified the system to the limit, to a lower level, seeing what can be done there, realized that not all see something depends on the structure, and are now beginning to complicate the structure and see what happens with the excitation waves which drugs will be effective which will not be effective.
Obtained pieces, patches of heart tissue, the question arises: if they are, maybe they can still somehow apply-first - is regarded as a model, and the second - to take and insert into the damaged area of ​​the heart.
Again, we do not come up with it first. Regenerative medicine heart, attempts to create implants at the cellular level for quite occur. But we began to approach that in order to effectively manage the structure of these implants. That is, by making nanofibers matrix and there put these cells.


There are certain difficulties if it is used for all three-dimensional wall: a thick layer of cells do not survive as long as it will not germinate vessels. Just a pile of folded layers of cells can not be: the top will live, and the lower die. Because not enough diffusion through the cell layers in order to come back oxygen and metabolites have gone from there, vessels there. So now there is a very complex area of ​​regenerative medicine, where researchers are trying to simultaneously raise and blood vessels, and heart cells. But everything is not so simple: you grow a piece of cloth that has a good vascular bed, but it will not match the vascular bed, which is the recipient. Microsurgery able hemming vessels, but here that much hemming-Still thin layers may also be used. For example, when damaged cardiac conduction system, discontinuities arise waves due to an obstruction, rather thin layer can ensure the smooth conduct of the waves. It is in this direction that we're trying to work. In cardiac cells have two main functions: the conduction of excitation and contraction. Excitation serves to cells were synchronized in sequence "orchestrated". If they decline chaotically come that same fibrillation. 95% of the heart can be perfectly healthy, fine cells and the heart ceases to perform its function. This is exactly why one time died athletes after training (the so-called sudden death syndrome) fibers of the heart are reduced fine, but not coordinated. To combat this, just provide defibrillators to shibanut electrocuted clear system of a pathological condition to further cells together again began to decline. That's why defibrillators hanging everywhere, though I do not very much seen as they are applied in reality. In the work of the heart is very important that excitement ran through and gave the signal to the cells, when they should be reduced.
When these findings are applied medical-
You've got to make predictions, and it is a thankless task. If we talk about issues related to regeneration, it is a long process. First you need to establish 100 percent technique, and then go to animal models - at least in rats hemming something that they survived. The first experiments have already been in the past year. Kemerovo colleagues, we conducted experiments on rats, and they lived with implants. Optical study we were not able to do because all the equipment was difficult to carry there, went without a redundant elements, and there is something not working.
Regenerative medicine, at least in Russia - this is not the next few years. With the walls of the heart, if all goes well developed - it 3-4 years of work.
When everyone is waiting for you in a year and a half betray something - this is madness. At the same reason as follows: the more money you give, the faster will. How sad we were joking, if a woman is to offer a million dollars does not bear a child for 9 months, and 2, it is unlikely anyone would agree. And someone said, "Why, anyone would agree, and then say that I could not."
As for the test pharmaceuticals, if it worked fine and all connections have been established, I think it is a year and a half or two. Creating a model system with which developers can work it the near future.
You mentioned research departments in major Western corporations. And Russian companies are interested in your research-
Any developers are extremely conservative. Those who engage in exploratory research, by definition, have to be more agile and have an open mind, not to miss something new just because it does not fit into the concept. And there people crushed business risks, it's not a grant, but the real work, experimental design, for which we must pay.
We were lucky. In MIPT has biofarmklaster "North" and very active people. One time I was told that in Russia all clusters, such a fashion word "cluster". But this is not entirely true, this cluster - there is not a building, an association, a partnership of several agencies - MIPT, research institutions, pharmaceutical companies, medical institutions and other ... Among them is the Center of High Technologies "KhimRar." Its director Andrey Ivashchenko - PTI graduate, head of the department in MIPT "innovative pharmaceutical and biotechnology", creating one of the ideologists of the CBF "North." We had already crossed several times, and the people who work with him, evince interest in the activities of our laboratory. We begin collaborations, now with his fourth-select department. We aim to ensure that the results of our work came in "KhimRar."
With pharmacists often works swarming-effect. It's like insects: worth one sniff and run attractor, all others run after him. For America, this is very common. When I got there, the mother of American professors explained to me: "In this direction, now nobody does anything, but if someone will show something that will run all there." This is often the case. Then, of course, there is a race for survival. Somebody wins, and the rest, of course, do not die, but wait, where you can still be able to run. It is very important to have someone show an example of use, this usually happens after a breakthrough.
And your sensational interview Pozner, in which you said that soon people able to pay $ 10 million for the complete rejuvenation of the body, will live forever, did not cause a similar effect-from Abramovich has not called-
From Abramovich - no.
Me interviewed by some foreign heads of state, but I had to disappoint all.
I can give a lecture, talk, give coordinates S.Yamanaki or write a letter to him, but not anymore.
Terrible thing: I was told that people use my name and trying to make money, some clinics have emerged that allegedly by my method works. Bullshit.
Our conversation with Posner was more philosophical. I'm not a young man, and I'm interested in issues of life - in general. I was very inspired by the success of scientists in Japan, he felt that there is a revolution, a revolution. And wanted to draw attention to this.
If a little more touch sensational topic. From your words about clear how the body will be updated, and whether the brain involved in all these processes-How can refresh the nervous tissue
One of the great neuroscientists said that the retina - is the brain which is submitted to the periphery. In fact, the retina - is neural tissue. Japanese have created it and transplanted made famous patient, who then became something to see. So that nerve cells can create.
Another question we have is very difficult to arranged a system of thought, memory, and so on. With the heart of everything is easier in the long run - it's a pump, very subtly arranged, but the pump. And the aging brain - it's no problem, I recently met data that animals have shown that preparations of brain cells live much longer than the animals themselves. That is, we are not limiting the brain - nerve tissue can survive long enough, people do not die from it. Eventually die from that stops the heart stops pumping blood, then brain cells die from oxygen starvation - that the mechanism of death. Now doctors accepted criterion for the indicator off the life support system - is brain death. And in fact, if all stored in the body, the brain cells live a long time if they are not bad vodka and poison the environment and not to hurt any kuru-kuru.
That is, after all mankind will live longer-
Will. It's already live longer. Statistics, of course, a little mischievous, there include infant mortality, and it turns out that the average age was once 35 years old, and now at 70.'s Not entirely true. Nevertheless, simply walk through the old European cemetery and look at what age people usually died in the XIX century, and in which die now. In the XIX century it was perfectly normal in 60-62 die, and now for the non-marginal 60 European small - not a conversation. Why the French are so eager to retire too late, to enjoy life in full, do not survive, and vice versa.
That is, after 20 years, if the system updates the human body is working, we will have the golden generation, which in 60 years will retire after this for a long time to live
I think retirement in 60 years or less justified when a person engages in some hard and unpleasant work. If work is so destroys a man, that he seeks crook put it down and lose much financially: retirement is nowhere on the level of wages, in any affluent countries.
There is another vector of development: the people are becoming more and more interesting and comfortable. In the States, I've seen people after retirement go to work: someone does not have enough money, and someone just wants to sit at home. I talked with an older school bus driver. It turned out that he was a former military pilot. He likes the work: children younger than it feels, feels its importance. How it all and throw to retire-And what vodka-drinking or poking around in the beds, the average Russian pensioner
Therefore, the retirement age - this is an opportunity to go for lower paid or volunteer work, but some work needs to be addressed. Therefore, raising the retirement age, which is trying to serve as a kind of horror, I do not consider those. You have to understand the relativity of all.
Recent years I have worked in Japan. My Japanese friends professor - about my age, there are older. There is a mandatory retirement at a university professor 62 years, sometimes with a delay of up to 63, if the person performing certain administrative functions. This is an absolute injustice and absurdity, because the Japanese sports without bad habits at age 62 - it is quite a young man, why should he leave the professors I know, the heads of the institutions, of the deans ... But why professors of this rule was once accepted for public servants. Civil servants retire and go to work in a taxi cab drivers out there - very intelligent, respectable people, usually former senior officials. There are Japanese category, which runs the world with cameras - something we do not. If in Japan postponed retirement or made it optional, many university professors, speaking in Russian, candles would put - there also would put candles, but in their temples. One of my good friend, a distinguished professor in a private university moved: there 70 years they can work. In the U.S. there is no such, there and in 80 years, if mastered, can work.
Are there any limits to refresh the body or theoretically it can be repeated infinitely
Well, no one has tried it, how many people survive updates. Of what is now understood about the reprogramming of cells, like no telomerase is no limit. In fact, the clock can be reset and start again.
But still need to check. Now beginning of the path, it may still not work.
At one time, when antibiotics are opened, there was a feeling that infectious diseases will be no more. As you can see, they still exist, and antibiotics should be changed so that they remain effective.
Do you think that all mankind need life-lengthening
I have a feeling that as it will, so be it. I think so. Because many people, I know of to his advanced years retain clarity of thought, their pity to lose. Therefore it is necessary. If someone does not need it will ease, break - not to build.
In addition to your laboratory, somebody in Russia is still engaged pluripotent cells
Yes. Those involved in the Institute of General Genetics, we worked together, we have a joint project. There are very serious people, such as Sergei L. Kiselev. Yet there are centers of stem cells, but I'm not quite aware of what they are doing.
From the standpoint of science - everything just happened. Pioneering work S.Yamanaki - is 2007. He quickly won the Nobel Prize - 5 years after opening, they are usually given 20 years, when all the foundations. It is necessary for these studies throw money very literate people gather.
In Russia, living islets science few accounts from one to another long swim. No single environment.

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