"Patches" on the heart: an ordinary miracle of bioengineering

Interview with Emil Ruvinov
Maria Horovets was talking, NEWSru.co.ilIn August of this year, the journal Proceedings of the National Academy of Sciences (PNAS) published an article about a project by a group of Israeli bioengineers and physicians who used "patches" on the heart from tissue grown in the patient's body to improve cardiac function after a myocardial infarction.

The results of this study were reported by all major Israeli and many foreign media, who described it as a genuine revolution in medicine. Our editorial board has received several letters from readers asking for more information about this study.

The study in question is conducted by a large group of scientists, including Dr. Tal Dvir, Professor Smadar Cohen, Dr. Jonathan Lior, as well as Alon Kedemb, Emil Ruvinov, Oren Levyk, Inbar Freeman, Natalie Landa, Radka Holbova, Micha Feinberg, Shani Dror and Yoram Etzion.

On the recommendation of Professor Cohen, correspondent NEWSru.co.il I met with the employee of the research group, the repatriate Emil Ruvinov, who is a graduate student of the Department of Biotechnological Engineering and the Faculty of Natural Sciences of Ben-Gurion University in the Negev, Beersheba.

The young (32-year-old) talented biotechnologist performs his scientific work under the guidance of Dr. Jonathan Lior, head of the Neufeld Cardiac Research Institute at Tel Aviv Sheba Medical Center (Tel a-Shomer), and Professor Smadar Cohen, head of the Department of Biotechnology at Beersheba University. In an interview NEWSru.co.il Emil Ruvinov talks in detail about the research, about the profession of bioengineering and about the prospects of this young science in Israel.

How is your research different from all the previous ones? What is its meaning and why can it be considered unique?

There are a lot of studies that try to repair damaged tissue after a heart attack or heart attack. We also created a kind of fabric – and this is the peculiarity of our research. The similarity of the tissue is grown in the abdominal cavity. This made it possible to create blood vessels in it. Then it was implanted on the heart.

Is the idea of such a "patch" implemented for the first time?

No. The idea of creating a "patch" is not new in itself. A lot of researchers are engaged in creating some kind of tissue in the laboratory, which is then transplanted to the heart. The goal is to restore an area that is not functioning after a heart attack.

What is new is the idea of creating a more functional fabric. Even before the "patch" created in the laboratory reaches the heart, it already has functional elements that provide blood flow. All the previous "patches" were just cells artificially grown in the laboratory and transplanted.

By its structure, the composition of the "patch" you created is as close as possible to the composition of the heart muscle, right?

Yes. Because there may be an influx of blood in our "patch". Blood flow significantly increases the likelihood that new, artificially transplanted cells will take root.

Is a "patch" a microscopic piece of fabric?

Yes, it's only a few millimeters. Approximately 5 millimeters in radius. And there are a lot of blood vessels in this very small area of tissue.

How is the "patch" sewn on the heart? How does it take root? Are each vessel "patches" sewn to the heart vessels?

This is preceded by painstaking laboratory work. The cells are placed in a polymer matrix. We set a goal: to create a tissue in the laboratory that already has a three-dimensional function even before transplantation. Usually the cells are placed in such a "box" where they grow in a row. We have found a technological solution for creating three-dimensional tissue in the laboratory. This is what distinguishes our work from most of the previous ones.

The fact is that if we want to change or strengthen the tissue of a living organism, no matter what... three-dimensional tissue is much more effective than just a series of cells. Therefore, a three-dimensional matrix is created, which allows you to grow cells in a three-dimensional volume. This is a relatively new area. We were among the first to start working on improving this technology and achieved some success in our work. The three-dimensional technology of cell growth makes it possible to use the resulting "patch" much more efficiently. Because the resulting fabric resembles a natural one.

Then the cells grown in the laboratory are transplanted into the abdominal cavity. In the abdominal cavity there is a process called angiogenesis. This is the process of creating new blood vessels.

The results of the laboratory work were tested on rats. We simply left a "patch" in the animal's abdominal cavity: after that, the rat lived quietly for a whole week.

Cells don't grow, but they form more and more blood vessels, right?

Exactly. And then, a week later, along with the blood vessels that appeared there, this "enriched" tissue is transplanted to the heart that suffered as a result of a heart attack.

A seam is made to fix the "patch" on the heart. Over time, the fabric takes root. Then everything happens by itself, due to the work of a living organism.

A miracle?

Well, that's a strong word. But, in principle, yes.

"Patches" are grown relatively recently. The creation of new tissues in the laboratory is a relatively new area and is now very popular. This is regularly reported by the media, it has become "fashionable".

In our study, we tested not only the creation of tissue, but also its stay in the abdominal cavity for a week. The technology of our work was aimed at enriching the future "patch" with blood vessels, which dramatically increases the survival rate.

That is, the survival rate of artificial tissues is the main problem?

The main problem is that any cells – whatever they are – require oxygen to exist. We can make a huge "patch", but if there is no oxygen in it, it will die almost instantly.

When does your group plan to test its "patch" on humans?

Any conceptual approach, before it is tested on humans, must undergo a variety of checks.

The article about the results of your research was submitted to the PNAS journal in December last year, about six months before publication. How much progress has the study made since then?

This is not a completely correct question. Our research and others like it belong to the category of basic science, research at the basic level, pure science. The purpose of such studies is to prove a concept or to find a new research approach. There is a very serious period of time between proving a new approach and testing it in humans. Not in all cases, new techniques reach people.

But do you plan to continue working in this direction?

As far as I know, not in the very near future. But in the future, everything can be.

It will take a long time before new tissues are used in medicine. A lot of ideas are eliminated. Do you know any statistics on this issue? How much time passes in Israel between the birth of a productive idea and its practical implementation?

If we are talking about the production of a new drug, then it may take 5-10 years from the proof of a new idea to its implementation. The percentage of those drugs that go all the way through development and testing to the end is absolutely minuscule. I don't know the exact data, but intuitively it seems to me that if only one out of 100 ideas of a new drug reaches production, then this is a very good result. At the same time, it still needs to be sold.

Would it be a mistake to say that most of the research in the field of bioengineering is related to the work of the heart?

Maximum efforts are invested in those areas that are the most necessary. Heart disease is the first factor of mortality in the world, it is a global problem. Although in Israel, cancer has already overtaken heart disease. But in any case, this is one of the two most serious problems of modern healthcare. This explains the huge attention and large investments in this area.

Is bioengineering a relatively new field of science?

I think this direction appeared about 20 years ago. Over time, the idea of creating a similarity of tissue in the laboratory was born. Cell research and attempts to grow cells in artificial conditions have been undertaken before. But over time, tissue engineering – the creation of tissues in laboratory conditions – has become a separate field that is rapidly developing.

There are two components in this area. Firstly, these are the cells themselves, the future tissue that they are trying to obtain in the laboratory. Secondly, this is the environment in which such cells are grown. Because in the previous conditions it was impossible to grow viable tissues. To create tissue, it is not enough to grow cells. It is necessary to create a habitat that will allow the fabric to become three-dimensional.

That is, there is a need for a technology that allows cells to be grown three-dimensionally.

Can we say that in the field of bioengineering, Israel occupies a leading position in the entire Middle East, and possibly in the world? In principle, in everything related to research, Israel is one of the first places in the world.

And this is despite the fact that the budget allocated for these studies is very small. There are several leading research groups in Israel that are working on the creation of heart tissues and other organs.

Who conducts such research – universities or hospitals?

Bioengineering is an interdisciplinary field. This is very important for understanding our work. Because, on the one hand, an engineering approach is needed here, and on the other hand, a deep knowledge of biology is required. Knowledge of production technology, for example, polymer technology, should be combined with the ability to perform complex calculations, such as calculations of oxygen passage. On the other hand, it is necessary to know the biological processes taking place in the cell. If we are talking about the treatment of diseases, knowledge of physiology and medicine is necessary.

Such studies require specialists in each specific field, it will not work individually. A combination of many disciplines is needed to create functional solutions. Research is conducted, of course, at universities. But each research group, it seems to me, works in cooperation with a large medical center, on the basis of which such studies are conducted. At the same time, part of the research group is doctors. That's exactly how it was with us.

You have touched upon the issue of budgets. How is it possible to conduct such large-scale research with insufficient funding?

I think that enthusiasm plays a very big role here. People believe in what they do. Of course, the ability to get grants in addition to existing funding is also important, but in order to get them, you need to constantly prove the productivity of research.

Are there many "Russian" repatriates among Israeli bioengineers? Can we say about this area that it is a "Russian" discipline?

It's hard to say. I think there are "Russian" researchers, but their presence is not as noticeable as in some other sciences. I don't think that similar studies were conducted in the Soviet Union. This is a relatively new discipline. But I believe that there are repatriated doctors who work in the field of biotechnology, and, of course, students who study this discipline here in Israel.

Can you name any research or discovery in the field of biotechnology that has had a strong impact on your activities and understanding of this discipline?

I can only judge about my field: research of biotechnologies for the treatment of heart diseases. Large-scale research is relatively rare, although there are not so few of them. Periodically, scientific articles are published, reading which, you think: "Amazingly interesting!". But I treat them rather as part of a general process: there must be some incentive for this area to constantly develop. I also follow the materials in the field of biology, there are also breakthroughs there. Basically, they are related to the fact that the main efforts of scientists are focused on everything related to tissue repair. If we are talking about the heart, then this is the restoration of tissues after a heart attack. This is a very dynamic area in which something new is constantly happening. Each time the research becomes more complex and more effective.

How did you get into bioengineering?

I studied at Tel Aviv University, having received a postponement from the army: I graduated with a first degree in biology. Then he joined the army and at the same time began studying for a second degree in medical sciences (not to be confused with training as a doctor), Department of Physiology and Pharmacology at Tel Aviv University. And he joined the Department of Bioengineering at the University of Beersheba as a graduate student. There is a first degree course in bioengineering at the University of Beersheba. But I myself came to this science in a slightly different way.

Who is your supervisor?

Professor Smadar Cohen, an employee of the University, and Dr. Jonathan Lior, an employee of Tel a-Shomer Hospital, who was my supervisor back in Tel Aviv when I was writing my master's degree. He brought me to Beersheba. Together with Lior and Cohen, I worked on a study, the results of which were published in the journal PNAS.

What caused the fashion for the specialty of bioengineering?

I think that fashion is caused, first of all, by the fact that this area is developing very dynamically.

What does a person who has received a first degree in biotechnology do?

He can continue his education or go to work: this may be a job in the field of pharmacology or assistance in research. It won't necessarily be a lab job. A graduate can work in production and engage in purely engineering aspects, where an understanding of the processes occurring in the cell is required. For example, during fermentation.

There are several areas in biotechnology. For example, the production of medicines or the production of bioreactors. There are theories in this area (production of bioreactors), it is a separate industry. The production process is one of the aspects of biotechnology. There is also a research direction.

And why did you decide to stay at the university and write a doctorate?

To be honest, I stayed at the university because I couldn't find a job. More precisely, I didn't find anything interesting enough for myself. The Israeli biotechnology market is not very large. Therefore, when applying for a job, the requirements are constantly changing. For example, when I was looking for a job, at least a completed doctorate was required everywhere. And a few years later, a person with a second degree could take the same job and the same position.

Are you saying that the requirements in this area are constantly increasing?

No, they change. In accordance with the general situation in the economy. Like in high-tech.

Can we say that a sharp demand for bioengineers is expected in Israel in the coming years?

I think this area is still developing. We are far from the maximum saturation of the market, after which the demand for specialists will begin to fall. Unlike high-tech, bioengineering has not yet reached its peak.

As for the research work... What is happening now in the field of scientific research may be needed only in five years. But this does not mean that our work can be postponed. Some theories we can't test at the moment. Some of them will even be laughed at. But it is likely that in 40 years these studies will bring their authors the Nobel Prize.

Portal "Eternal youth" http://vechnayamolodost.ru22.09.2009