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00:12:06regenerative medicine, about cell therapy, and whether
00:12:09stem cells can help us live to 120 years. And our guest
00:12:13is Anastasia Yulievna Yefimenko, Doctor
00:12:16of Medical Sciences, Professor of the Russian Academy of Sciences,
00:12:19head of the laboratory of tissue repair and regeneration, center
00:12:23of regenerative medicine of the medical
00:12:26scientific and educational institute of Moscow State
00:12:30University named after Lomonosov. Hello,
00:12:33hello, can we dot all the i's and cross all the t's: stem or
00:12:37progenitor cells? Stem cells, of course,
00:12:40stem, but in this situation it's not so important how they are pronounced,
00:12:44what's important is what this term hides. Anastasievna, you understand everything,
00:12:47but someone who is listening to us may not
00:12:51understand, what is regeneration? It's restoration, restoration.
00:12:55I hear the term regenerative medicine for the first time, is
00:12:59it some new field, right? It's a very, very new
00:13:02field, you're absolutely right, especially before our show, I even
00:13:06bothered to find out when this term appeared in discourse,
00:13:09yes, it's the very beginning of the 2000s, meaning it's
00:13:12a very, very young science and even more so a branch
00:13:16of medicine, although of course it
00:13:20stands on the pillars, on the foundation
00:13:22of cellular achievements...
00:13:28century without the discovery of understanding how a cell is organized and how it looks
00:13:32and how to work with a cell outside
00:13:34the body, how our DNA looks and what
00:13:38is produced from it in the cell, yes, what determines how
00:13:42a cell looks, its phenotype, yes, the realization of the genetic
00:13:46program embedded in it, and understanding how
00:13:49cells communicate with each other and how they implement those complex
00:13:53programs, yes, which...
00:13:55in ontogenesis, in the program of individual organism development, we have
00:13:59all this knowledge formed the foundation for
00:14:02regenerative medicine, which is sometimes called the medicine of the future,
00:14:06because it offers fundamentally new
00:14:09solutions for medical science and for
00:14:12medical practice. Its novelty, probably,
00:14:15is described in very simple words,
00:14:19traditional medicines can treat
00:14:23one specific.
00:15:25new cells must form in their place, and you all know the record-holding organs for
00:15:28producing new cells, for example, blood cells, it's the bone marrow, it works throughout
00:15:31life, literally producing - there are
00:15:35other tissues in our body that
00:15:41renew and regenerate very well, these are coverings,
00:15:44these are mucous membranes, but there are organs that do this much
00:15:48worse, more slowly, don't prompt me, it's the liver, bone
00:15:51marrow, bones, that is, for example,
00:15:55there are organs that practically do not
00:15:57renew throughout life, this is the brain - this is
00:16:01the myocardium, this is what
00:16:03the development of very serious diseases is connected with.
00:16:38try to shift them towards stimulating
00:16:42recovery, stimulating the regenerative potential that is
00:16:45inherent in us. I should probably
00:16:48clarify that when we talk about the processes
00:16:52of forming new cells in place of dead or lost ones, this is
00:16:55far from only the formation of new cells and stem cells, which everyone knows
00:16:59and everyone likes to talk about. One of the most common mechanisms
00:17:03for the formation of new cells is what we all
00:17:06learn in school. Yes, cell division from
00:17:09pre-existing ones, that is, specialized cells with their own
00:17:13function divide under the action of factors coming from
00:17:16the damaged area and replace the population
00:17:20that needs to be replaced.
00:17:23However, with sufficiently serious damage, yes, just
00:17:27now on the screen we have an example of a dividing cell, you see it has two blue
00:17:31nuclei, and soon it will divide its cytoplasm too, and this
00:17:34mechanism works very well for replacing
00:17:38small damages for constant tissue renewal,
00:17:41for normal
00:17:44physiological existence, in the case of sufficiently
00:17:48serious damage, this process cannot provide
00:17:51the formation of the required number of cells, then we have to use
00:17:55our golden reserve, stem cells, it must be said that we have them in all
00:17:58tissues and organs, they are preserved during
00:18:02development, and after birth remain in
00:18:05a very small number, and in specialized places
00:18:09provide the formation of new cells
00:18:13during differentiation or specialization, that is, the stem
00:18:16cell itself is not defined as a cell
00:18:19type, but it can move in several directions depending
00:18:23on the needs of the tissue, this is such
00:18:27a cellular fate, specializing in the end,
00:18:30acquiring a phenotype, yes, that is, those properties that will define
00:18:34its function, these stem cells...
00:18:38do they live some kind of their own life, do they multiply somehow, or
00:18:41are they given to us at birth, and we, so to speak,
00:18:45try to preserve them in ourselves? This is
00:18:48a very good question, to which it's not so easy to give
00:18:52an answer, because as I already said, our different tissues and
00:18:55organs renew at different rates, so in some
00:18:59tissues the set of stem cells is activated quite
00:19:02often, for example, well, in the same skin there are at least five
00:19:06or six types... there is a hair follicle
00:19:16next to it, there is its own subtype of stem cells, they
00:19:19work quite often and actively, because
00:19:23the skin renews actively, the same can be said about stem cells
00:19:27of the intestine, the intestinal mucosa renews quite
00:19:30actively, yes, therefore stem cells there, well, so to speak,
00:19:34work often, at the same time... in many
00:19:38other organs tissues there can be
00:19:41silent stem cells, and it is generally believed that a stem cell by
00:19:44definition should be at rest and its environment
00:19:48ensures this rest, only in case of damage it
00:19:51should activate, begin to divide, begin
00:19:55this process of specialization, differentiation.
00:19:58There were interesting studies when in very long-
00:20:02lived people, centenarians, that is, people living over 100 years old,
00:20:05they studied through complex molecular
00:20:07genetic analysis how many stem cells in the bone marrow
00:20:11activated to give rise to blood cells, these are hematopoietic
00:20:15stem cells, which differentiating
00:20:18give erythrocytes, leukocytes, yes,
00:20:21megakaryocytes and platelets in them, these
00:20:24cells, as it turned out, in a woman, if I'm not mistaken,
00:20:27114 years of life, activated only a few, that is, the
00:20:31progenitors of all her blood cells throughout her life were
00:20:35only a few, a very interesting story:
00:20:37but how this happens in other tissues, this is a very
00:20:40difficult research question, we also have a third
00:20:44mechanism, which was discovered relatively recently,
00:20:48already in the 21st century, many researchers began
00:20:51to talk and write about it, this is the mechanism of transdifferentiation,
00:20:55the transformation of one type of mature cells
00:20:58into another, while, of course, it is necessary to seriously
00:21:02reorganize, and return from the point of view of implementing the genetic
00:21:06program, such a more undifferentiated, more
00:21:09unspecialized state, now many researchers
00:21:13are engaged in the question of how close this intermediate
00:21:16state is to a stem cell during transdifferentiation,
00:21:20or there are mechanisms of transition, change of phenotype
00:21:24of one cell type to another, which is now
00:21:28more needed by this tissue, that is, at some
00:21:31moments ordinary cells, for example, skin cells
00:21:35under the influence of some circumstances
00:21:37can become bone cells, rather, this process is
00:21:41well described when skin cells, epithelial
00:21:45cells, turn into cells more similar to connective
00:21:48tissue cells, because they are better, then they can move towards
00:21:52the damage and replace
00:21:55the defect that has arisen, and this happens without the involvement
00:21:58of stem cells, one specialized cell
00:22:01turned into another type and function cell.
00:22:05There is such a graph when I show that an excess of fatty tissue
00:22:09and a lack are absolutely equally
00:22:11unacceptable. We know that fatty tissue is a factory for
00:22:15producing a huge amount of all sorts of vital substances, but is this
00:22:19history not also connected with the fact that fatty tissue is a great
00:22:22source of stem cells? This is a wonderful
00:22:26example when the idea of stem cells, yes,
00:22:29is formed on the basis of some kind of, do not
00:22:32be offended, only a layman's understanding of cell therapy, why do you
00:22:36talk about fatty tissue? Well, surely, because you read in many
00:22:39publications that for cell therapy, for regenerative medicine,
00:22:42fatty tissue cells were used, but they were used not because
00:22:45there are so many of them or they are somehow special, but simply
00:22:49because.
00:23:05used for regenerative medicine
00:23:08as a drug, yes, as a therapeutic agent, and they are somehow
00:23:11associated with the wall of blood
00:23:15vessels, respectively, in a well-vascularized tissue, there are more of them per gram
00:23:18of tissue yield. This is the only reason why
00:23:22fatty tissue is very often used, while
00:23:26it is well known that in all, in
00:23:29all tissues there are these subpopulations, that
00:23:33is, a small number of stem cells, which we call tissue-
00:23:36specific, yes, that is, they are intended for the restoration
00:23:39of this particular tissue, and perhaps I will allow myself such
00:23:42a generalization, if there is an opportunity in a direct
00:23:46comparative experiment to use one's own
00:23:49non-specific cells, uh-huh, cells of the
00:23:52same fatty tissue or bone marrow, which are also quite
00:23:56easy to obtain, then usually tissue-specific cells are better,
00:24:00but isolating them and making medicine from them is very often
00:24:03not easy, especially if it is some
00:24:06hard-to-reach organ from which you can't just take a biopsy, right?
00:24:10Well, of course, then they take instead
00:24:13more easily accessible sources for cell
00:24:17therapy.
00:24:21here somewhere they are actively printing thoughts about how soon
00:24:25you won't have to deal with teeth at all, because
00:24:28don't throw them away,
00:24:31they say, from them they will extract stem cells
00:24:35and then replace your whole jaw, yes, like a
00:24:39garden, is this fantasy or can we
00:24:42already prepare? It's true, teeth,
00:24:45especially good healthy teeth
00:24:47without damage. which are
00:24:50removed, for example, sometimes even in adults, wisdom teeth are removed
00:24:54due to their incorrect
00:24:56position, and I won't even mention baby teeth, they are an excellent
00:25:00source of stem cells, they are called stem
00:25:03cells of the pulp, or stem cells are also isolated
00:25:07from the ligaments surrounding the teeth, they have
00:25:10a specific origin during embryogenesis, they
00:25:14have a slightly different origin than many stem cells of other
00:25:17organs, they have an advantage in
00:25:21how they can divide, that is, build up, yes,
00:25:24similar ones for cell therapy, and there are some
00:25:27advantages in terms of the ability to specialize in a certain tissue,
00:25:31for example, in bone, cells from the pulp
00:25:34of a tooth are an excellent source for restoring
00:25:37hard bone-like tissues, including for
00:25:41jaws, for example, or even for long tubular bones, they are very
00:25:45actively used, so yes, it is a very good source, the only thing is that they
00:25:49need to be very, very quickly brought to a laboratory that
00:25:52powerful cells. Well, how to store baby teeth for
00:25:55the future, or is it just
00:25:58that you need to find a partner, a place where
00:26:02your wonderful stem cells can be isolated and preserved,
00:26:05and this is already a question concerning proper biobanking
00:26:09of cell collections, this is a separate very interesting field,
00:26:12closely related to regenerative medicine, because
00:26:16without proper preservation of cell
00:26:19lines, cell populations, the development
00:26:22of our field is difficult to imagine, therefore
00:26:25specialized laboratories and specialized
00:26:28banks, biobanks, are needed where such material can be processed.
00:26:34Look, what our listeners will hear: now
00:26:37we go to the dentist, immediately extract teeth, look for
00:26:41a laboratory that will preserve them for us, so that later, yes,
00:26:45but this is not streamlined, a person cannot
00:26:48just come and store these teeth, it's also pointless to store these
00:26:52teeth now, so this is, let's say, a perspective
00:26:56for some time, someday, just like now we go to the laboratory, donate blood,
00:27:00someday a person will say: tomorrow I'm going to have a wisdom tooth extracted,
00:27:03please, I don't know, give me
00:27:07a container in which I will bring the tooth to you
00:27:10and you will then preserve my cellular
00:27:13material, it's the same as with umbilical cord blood cells, yes,
00:27:17I believe that we can absolutely calmly talk about
00:27:20preserving cells from the pulp as also a kind of biological
00:27:23insurance, it's just that now, unfortunately, in our country, as you rightly say, it's not
00:27:27streamlined, I think it's not streamlined in the
00:27:30world either.
00:27:32Not in the world either, yes, well, let's say, I, I don't know,
00:27:36froze teeth
00:27:39or something else, can
00:27:42I give my biological material to
00:27:46another person who needs it more,
00:27:49or will it not work like that? Let's
00:27:53break your question down into two components. The first component
00:27:56is bioethical, uh-huh, if you are responsible for yourself, if you
00:28:00give voluntary informed consent?
00:28:13from one person for the treatment of another person's disease, this is an absolutely correct and normal
00:28:16story, in fact cell therapy is divided
00:28:20into autologous, when a patient can be treated with
00:28:23his own cells and products created from his own
00:28:26cells, or allogeneic, when he receives cells
00:28:30from donors, in fact examples of allogeneic...
00:28:40you all know well, it's bone marrow transplantation, uh-huh, which we consider to be the first technology of regenerative medicine and date back to 1968 the beginning of such
00:28:43medical, scientifically based application of stem cells for
00:28:46tissue regeneration, well, in this situation,
00:28:50yes, allogeneic autologous cell
00:28:54therapy is justified in certain cases and has its own
00:28:57advantages and disadvantages, well, if briefly, autologous therapy
00:29:00is undoubtedly this...
00:29:32since functional capabilities, this very regenerative potential, this is
00:29:36shown in a very large number of studies, it worsens,
00:29:39then treatment with one's own cells can be much
00:29:43less effective than it was shown and assumed in an experiment, for example.
00:29:46In this sense, allogeneic therapy may
00:29:50be more advantageous, that is, cells from a young,
00:29:53relatively healthy donor who has given his consent can be
00:29:57used in this case. In addition, allogeneic therapy has another
00:30:00significant advantage. You can produce this
00:30:04product in advance, check its safety, quality, its
00:30:08effectiveness, and then, when the patient comes, you can
00:30:11request this product from the bank and use it as
00:30:15prescribed, and for many clinical
00:30:18tasks, the time required to prepare
00:30:21the product can be a significant factor, so
00:30:25it can be used if there are indications.
00:30:28Did I hear correctly that in the treatment of
00:30:31oncology: cell therapy is now used, moreover,
00:30:35I would say that it is in the treatment of oncology, first of all, like
00:30:38hematological diseases, we are now seeing just a
00:30:42boom in new products, yes
00:30:45and then we go in the direction of autoimmune
00:30:48diseases, and here I wanted to ask, there are many
00:30:52interesting promising targets related to the fact that cells
00:30:55regulate the immune system's response to
00:30:59the emergence of foreign antigens, native cells, or when
00:31:03the immune system for some reason starts to react against its own cells,
00:31:07here the prospects for cell therapy are very great, it's
00:31:10not quite regenerative medicine, yes, it's more like
00:31:14cells. smart killers, however, as a
00:31:17therapeutic agent, as a medicine, these are living cells, and not
00:31:21just living cells, but also genetically modified
00:31:24in order to better recognize
00:31:28a tumor cell, these cells are
00:31:31from, as it turns out, well, that is, from the cancer
00:31:35patient himself, yes, they are suitable, they are suitable, yes, if
00:31:39you teach them in the right way, they are suitable,
00:31:43in our field.
00:31:45in such regenerative medicine, specifically aimed at
00:31:48controlling tissue regeneration processes,
00:31:52our medicine, it seems to me, is wonderful because we are not
00:31:56limited by any clinical direction, the
00:31:59mechanisms we are dealing with are universal for different organs
00:32:02and tissues, and can be applied to a very wide range of
00:32:05clinical tasks, well,
00:32:08I like to talk about our very
00:32:11valuable project for Moscow University.
00:32:15when from a fundamental idea, from a
00:32:18project to study stem cells and their functioning
00:32:22in tissues, I must say that this is a very
00:32:25difficult story, because we talked a lot about how
00:32:29unique properties stem cells must have, who ensures
00:32:32their preservation of these unique conditions in
00:32:35tissues, a special microenvironment, it is called
00:32:39the stem cell niche, so the existence of this niche
00:32:43in different tissues and organs. and regulation, very complex
00:32:47regulation between the components of this niche, this is a subject for
00:32:50fundamental study, so
00:32:53at the Center for Regenerative Medicine of Moscow State University, we are engaged in
00:32:56issues of just regulating lower stem cells, as a
00:33:00model we used the niche of spermatogonial stem cells, do not
00:33:03try to repeat a very complex term, but these are the stem
00:33:07cells that work to produce spermatozoa,
00:33:10ensuring the reproductive function of men, in case of damage
00:33:14like this... a block of spermatogenesis occurs and fertility
00:33:17is impaired, now this is a very, very serious problem,
00:33:21so we model such disorders of
00:33:24spermatogenesis in animals using various influences, look how
00:33:27small and atrophied the testis can be when damaged and
00:33:31how much the structure of the seminiferous tubules is disrupted,
00:33:35literally the production of specialized cells from stem cells is blocked,
00:33:38the testicle becomes so small when damaged, this is due to
00:33:42the fact that a - a block occurs at the tissue
00:33:45level, literally a block of the process of formation of
00:33:49differentiated spermatozoa
00:33:52from stem cells, and we showed that if on
00:33:56such models of damage we try to
00:33:59restore the niche normal microenvironment
00:34:03of cells, and we did this by introducing
00:34:06mesenchymal stromal stem cells into the testis
00:34:08itself, or not cells, but those biologically active factors
00:34:12that they secrete, we called them a secret, right?
00:34:24Below is a slide showing that even the mass of the testes recovers after a few months, and so does the function,
00:34:28remembering the tasks of regenerative medicine, the function is realized in
00:34:31the form of production of spermatozoa from stem cells, and not
00:34:35just spermatozoa, but motile ones, those that ensure fertility,
00:34:39in animals we see partial restoration of the ability to give
00:34:42healthy, normal offspring in men. You are great, you
00:34:46save girls,
00:34:49for girls it’s a bit different, yes, the situation is arranged,
00:34:52if in men these stem cells work throughout their lives to
00:34:56produce specialized cells, then in women, as you
00:34:59know, they are laid down at birth, then only gradually
00:35:03come out, are used, so there it turns out to be a somewhat
00:35:07fundamentally different story with the impact on stem cells,
00:35:11and this is not translated mechanistically, although of course we actively. regulation
00:35:19of this process also, that is, egg cells
00:35:22cells at all,
00:35:25it's more complicated, as I understand it, this is a slightly more complex
00:35:28story, although of course scientists are also actively working on it,
00:35:31this is primarily related to the possibility of
00:35:35controlling what is called the potency of stem
00:35:38cells, when we talked with you about the ability to
00:35:41differentiate, it actually differs in different types. of the body,
00:35:53their potency is reduced, it's clear why, because we don't need our
00:35:57cells to turn into anything under the influence of some
00:36:01sudden chaotic factors, but when it's
00:36:04an embryo, and even more so, when it's...