20 January 2017

When will we grow a new liver

Irina Reznik, MedNovosti

How to "grow" full-fledged biological human organs in the laboratory, will they be able to replace donor ones when such technologies become massively available and what mini-organs are needed for in the educational program from the director of the Institute of Molecular Medicine of the I.M. Sechenov First Moscow State Medical University, Professor Andrey Zamyatnin.

– Andrey Alexandrovich, is the cultivation of human organs really already on stream? Which ones are easier to grow, and which ones have problems?

– Alas, it's too early to talk about the flow. The creation of viable human organs is a very complex bioengineering technology. And carrying out such procedures, even with those organs whose cultivation is fundamentally possible and promising, is complicated by the high cost and complexity of the process. The most problematic in this sense are the liver, pancreas. Naturally, there are problems with the organs of the nervous system, which, due to their specificity, differ qualitatively from other organs. In these cases, too many intercellular connections are involved, and it is not yet very clear how these connections can be established using bioengineering technologies.

As for the liver, the problem is that there are certain limitations that determine the possibilities of organ regeneration. It has been noted that it is possible to regenerate the liver to a full-fledged organ only if at least a quarter of its part is present. The mechanisms of such restrictions are still not fully understood. According to the world leader in regenerative medicine, Professor Anthony Atala from Wake Forest University, there is probably some kind of regulation at the level of the body that determines the state of the organ and the degree of its viability, that is, the potential for regeneration.

To date, the greatest success has been achieved in the creation of organs with the least complex structure (skin, bones, cartilage), as well as hollow organs (bladder, trachea). However, the process of creating organs is not fully understood, and therefore there are a number of problems that are gradually finding their solution. It is also unknown (since it has not been studied) how safe the use of artificial organs is, and what consequences may arise during their transplantation, including side effects.

– And yet, how soon will these technologies become massively available? Today, thousands of people are waiting for a kidney transplant. Is there any hope that in the near future this will not require a donor organ, it will simply be grown?

– There is hope, but do not forget about the high cost of technology. Like any new product, a new technology initially has a high cost, even if you do not consider ethical issues. In the meantime, a donor kidney costs less than a grown kidney. Let's hope that soon the technology, and hence the artificial organs grown on it, will become more accessible.

There are isolated cases of transplantation of a "grown" kidney abroad. However, questions inevitably arise that are within the competence of the legislations of such countries, for example, related to permits for operations and ethical standards. We are talking, first of all, about choosing the source of the source material (cells) for growing organs, as well as about the problems associated with establishing boundaries between experiment and treatment.

– And what, in short, is the essence of technology? How is it possible to grow an organ separately from the person himself?

– Any organ consists of an extracellular matrix that performs the function of a connective tissue framework that gives the organ shape and density, as well as certain cellular components that fill it (mainly fibrillar proteins and proteoglycans) specific to each type of tissue. During the development of the organism, starting from the stage of the embryonic period, the extracellular matrix is created by its own cells due to the exchange of cellular components with the external environment. Accordingly, bioengineered technologies of "growing" organs should reproduce this process as close as possible to the natural one. And developers have to solve two main tasks: how to stimulate cells to form an extracellular matrix, and, in fact, how to preserve the viability of such cells in the matrix.

Extracellular matrix can be created from both artificial and biological materials. The main thing is that the cellular components of the matrix are viable, functional and, if necessary, capable of modification for the purposes of the developer. For example, a biodegradable artificial matrix is used, which should eventually dissolve, being replaced by a natural one.

Stem cells capable of self-renewal and differentiation (transformation) into specialized cell types are also used for growing organs. In a living organism, stem cells are involved in the processes of regeneration and restoration of damaged organs and tissues. The largest number of these cells are found in the bone marrow and adipose tissue, less in the skin, blood vessels, and muscle tissue. The main source of allogeneic (unrelated) stem cells is the umbilical cord blood of newborns, which is why programs to create cord blood stem cell banks are being actively developed in almost all countries of the world.

A new direction of regenerative medicine technologies has already been developed – 3D bioprinting, which uses technologies of three-dimensional bioprinting of organs from autologous (own) stem cells of the patient. The technology consists in developing a three-dimensional model of an organ and obtaining groups of cells in contact with each other to form a three-dimensional structure. Such groups of cells are the printed material for 3D bioprinting of organs.

– In addition to artificial organs needed to replace damaged ones, mini-organs are also grown for laboratory purposes.

- Yes. And this is a very promising scientific direction. In particular, mini-organs are used for drug testing (as an alternative to animal experiments), as well as in cases for which animal models do not exist (for example, in diseases associated with the immune system). Also, such an approach could help solve ethical problems associated with inhumane treatment of animals. For example, scientists have already learned how to "grow meat" of animals, that is, in fact, this is the cultivation of muscles from stem cells in a test tube.

As for technology, there is practically no clear boundary between organs and cells for laboratory practice. Various cells (model cell lines) have been used for decades, and now organ-like models are being "assembled" on their basis.

– Is there any specificity in cases when organs are grown for human transplantation, and when they are created for experiments?

– In both cases, the main goal is pursued – to achieve maximum identity. If this goal is not achieved, then in the case of transplantation, the grown organ will be rejected by the body. In the case of using the organ for experimental purposes, it will be impossible to assess the reliability of the results obtained, and therefore extrapolate the identified effects on the human body.

Andrey Zamyatnin is also the head of the Strategic Academic Unit (SAE) "Multidisciplinary Center for Clinical and Medical Research", which, in addition to training highly qualified personnel, develops biomedical products. In addition to the Institute of Molecular Medicine, the Center includes the Institute of Regenerative Medicine (Director Butnaru D.V.) and the Institute of Pharmacy and Translational Medicine (Director Tarasov V.V.).

Portal "Eternal youth" http://vechnayamolodost.ru  20.01.2017

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