Artificial bone marrow
Alexey Levin, Voice of AmericaBone marrow is a specific tissue that fills the cavities of bones in all vertebrates.
It is presented in two varieties. The red bone marrow, which in humans makes up about one and a half percent of the total body weight, contains hematopoietic tissue that supplies the body with new blood cells. Yellow bone marrow, on the contrary, is characterized by a predominance of adipose tissue.
Red bone marrow is preserved throughout life in the ribs, sternum, vertebrae and some other bones. It consists of specialized stem cells that give rise to all kinds of blood and lymph cells. Therefore, the red bone marrow serves as the main hematopoietic organ of our body. The activity of the immune system, which constantly uses white blood cells supplied by the bone marrow, depends on his well-being. The bone marrow also continuously renews the supply of red blood cells, which supply the internal organs with oxygen and free them from carbon dioxide.
Researchers from Michigan, together with colleagues from Texas and Florida, have just posted an article on the website of the journal Biomaterials describing artificial tissue that largely reproduces the work of living bone marrow. Professor Nikolay Kotov, its head, told the Russian service of the Voice of America about this project in an exclusive interview.
Alexey Levin: Nikolai, first of all, let me ask a deliberately naive question. Why was it necessary to invent and build a red bone marrow simulator?
Nikolay Kotov: Let's start with the practical benefits that can be derived from our development. Many medications, for example, anticancer and antiarthritis drugs, often suppress the work of the hematopoietic tissue of the bone marrow. This leads to many complications, including anemia and weakened immunity. Therefore, it is very important to check whether candidates for future drugs are toxic to the bone marrow even before their clinical trials begin.
Now, if such studies are conducted, then on laboratory animals. However, this is a very expensive pleasure. In addition, the physiology of mice, rats and other inhabitants of vivariums is by no means identical to human. The results that are obtained in such experiments cannot be automatically distributed to our own body. Therefore, we would like to have working laboratory models of human bone marrow on which experimental drugs could be tested quickly, in a unified and relatively inexpensive manner. Until now, such models did not exist at all. But we managed to create them.
A.L.: But the work of the bone marrow "in vitro" has been studied for many years, hasn't it?
N.K.: Yes, of course – more precisely, in Petri dishes. Usually, standard cassettes for 96 compartments are used in such experiments, in which cell cultures are grown. But this way it is possible to reproduce only simple cellular layers. And the hematopoietic cells of the bone marrow are embedded in a complex spatial tissue structure, within which they intensively interact with cells of other types. So a realistic model of this organ should also be three-dimensional. It is necessary to place the hematopoietic cells in approximately the same geometric and biological conditions in which they are in a living organism.
A.L.: And now it was possible to do it?
N.K.: Exactly. The hematopoietic structures of the bone marrow are embedded in a porous supporting tissue called reticular (as well as reticular). We should have invented such a porous supporting matrix, too. In addition, it had to be made transparent in order to then use optical microscopes for observations. We also wanted this matrix to be placed in standard cellular cassettes for studying cell cultures.
We have achieved all this. We have made a structure with a very tricky name – the inverted geometry of a colloidal crystal. Imagine a lot of identical balls densely filling a certain volume. This is the colloidal crystal. We made it out of tiny spheres, and then filled it with a special polymer. This polymer filled the voids between the spheres, while the spheres themselves dissolved in it. As a result, we got a material with a lot of tiny pores. It served as a replacement for the reticular tissue.
A.L.: As I understand it, hematopoietic cells were introduced into these pores?
N.K.: Exactly. We isolated such cells from the blood, where they are always present. However, it was necessary to create an appropriate biological environment for them. After many experiments, we selected stroma cells, unformed connective tissue, for him. To these we added osteoblasts, specialized cells synthesizing new bone tissue. Both osteoblasts and planar cells are present in the bone marrow and in its surroundings. In combination, they turned out to be a very good environment for hematopoietic cells.
A.L.: How did this manifest itself?
N.K.: Our artificial bone marrow has started working. We have seen that it is able to produce both different types of white blood cells and new hematopoietic cells. Perhaps red blood cells and red blood cells appear there. But it is too early to confirm this, additional research is needed.
A.L.: What other experiments were conducted?
N.K.: It was important to prove that our bone marrow simulator is able to get involved in the work of the immune system. We did this in two ways. First, we infected the artificial hematopoietic tissue with a weakened strain of one of the influenza viruses. As we had hoped, she began to produce antibodies to this microbe. In addition, we planted pieces of tissue in mice with a disabled immune system. It successfully took root, overgrown with blood vessels and began to produce a variety of human immune cells.
A.L.: It remains for me to ask the traditional question about plans for the future.
N.K.: Now we will work out practical problems related to the specific use of our model for toxicological studies. But there is another idea. I would like to use artificial bone marrow as a kind of factory for the production of hematopoietic stem cells. They give rise to all mature blood cells, but their capabilities are far from limited to this. It has now been proven that hematopoietic cells can be made to produce nerve tissue, fat tissue, and other types of tissues. This is a very attractive prospect, and we hope to realize it.
A.L.: In fact, it would be great. I hope that everything will work out. And thank you so much for an interesting conversation.
Portal "Eternal youth" www.vechnayamolodost.ru24.12.2008