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[00:12:06] regenerative medicine, about cell therapy, and whether
[00:12:09] stem cells can help us live to 120 years. And our guest
[00:12:13] is Anastasia Yulievna Yefimenko, Doctor
[00:12:16] of Medical Sciences, Professor of the Russian Academy of Sciences,
[00:12:19] head of the laboratory of tissue repair and regeneration, center
[00:12:23] of regenerative medicine of the medical
[00:12:26] scientific and educational institute of Moscow State
[00:12:30] University named after Lomonosov. Hello,
[00:12:33] hello, can we dot all the i's and cross all the t's: stem or
[00:12:37] progenitor cells? Stem cells, of course,
[00:12:40] stem, but in this situation it's not so important how they are pronounced,
[00:12:44] what's important is what this term hides. Anastasievna, you understand everything,
[00:12:47] but someone who is listening to us may not
[00:12:51] understand, what is regeneration? It's restoration, restoration.
[00:12:55] I hear the term regenerative medicine for the first time, is
[00:12:59] it some new field, right? It's a very, very new
[00:13:02] field, you're absolutely right, especially before our show, I even
[00:13:06] bothered to find out when this term appeared in discourse,
[00:13:09] yes, it's the very beginning of the 2000s, meaning it's
[00:13:12] a very, very young science and even more so a branch
[00:13:16] of medicine, although of course it
[00:13:20] stands on the pillars, on the foundation
[00:13:22] of cellular achievements...
[00:13:28] century without the discovery of understanding how a cell is organized and how it looks
[00:13:32] and how to work with a cell outside
[00:13:34] the body, how our DNA looks and what
[00:13:38] is produced from it in the cell, yes, what determines how
[00:13:42] a cell looks, its phenotype, yes, the realization of the genetic
[00:13:46] program embedded in it, and understanding how
[00:13:49] cells communicate with each other and how they implement those complex
[00:13:53] programs, yes, which...
[00:13:55] in ontogenesis, in the program of individual organism development, we have
[00:13:59] all this knowledge formed the foundation for
[00:14:02] regenerative medicine, which is sometimes called the medicine of the future,
[00:14:06] because it offers fundamentally new
[00:14:09] solutions for medical science and for
[00:14:12] medical practice. Its novelty, probably,
[00:14:15] is described in very simple words,
[00:14:19] traditional medicines can treat
[00:14:23] one specific.
[00:15:25] new cells must form in their place, and you all know the record-holding organs for
[00:15:28] producing new cells, for example, blood cells, it's the bone marrow, it works throughout
[00:15:31] life, literally producing - there are
[00:15:35] other tissues in our body that
[00:15:41] renew and regenerate very well, these are coverings,
[00:15:44] these are mucous membranes, but there are organs that do this much
[00:15:48] worse, more slowly, don't prompt me, it's the liver, bone
[00:15:51] marrow, bones, that is, for example,
[00:15:55] there are organs that practically do not
[00:15:57] renew throughout life, this is the brain - this is
[00:16:01] the myocardium, this is what
[00:16:03] the development of very serious diseases is connected with.
[00:16:38] try to shift them towards stimulating
[00:16:42] recovery, stimulating the regenerative potential that is
[00:16:45] inherent in us. I should probably
[00:16:48] clarify that when we talk about the processes
[00:16:52] of forming new cells in place of dead or lost ones, this is
[00:16:55] far from only the formation of new cells and stem cells, which everyone knows
[00:16:59] and everyone likes to talk about. One of the most common mechanisms
[00:17:03] for the formation of new cells is what we all
[00:17:06] learn in school. Yes, cell division from
[00:17:09] pre-existing ones, that is, specialized cells with their own
[00:17:13] function divide under the action of factors coming from
[00:17:16] the damaged area and replace the population
[00:17:20] that needs to be replaced.
[00:17:23] However, with sufficiently serious damage, yes, just
[00:17:27] now on the screen we have an example of a dividing cell, you see it has two blue
[00:17:31] nuclei, and soon it will divide its cytoplasm too, and this
[00:17:34] mechanism works very well for replacing
[00:17:38] small damages for constant tissue renewal,
[00:17:41] for normal
[00:17:44] physiological existence, in the case of sufficiently
[00:17:48] serious damage, this process cannot provide
[00:17:51] the formation of the required number of cells, then we have to use
[00:17:55] our golden reserve, stem cells, it must be said that we have them in all
[00:17:58] tissues and organs, they are preserved during
[00:18:02] development, and after birth remain in
[00:18:05] a very small number, and in specialized places
[00:18:09] provide the formation of new cells
[00:18:13] during differentiation or specialization, that is, the stem
[00:18:16] cell itself is not defined as a cell
[00:18:19] type, but it can move in several directions depending
[00:18:23] on the needs of the tissue, this is such
[00:18:27] a cellular fate, specializing in the end,
[00:18:30] acquiring a phenotype, yes, that is, those properties that will define
[00:18:34] its function, these stem cells...
[00:18:38] do they live some kind of their own life, do they multiply somehow, or
[00:18:41] are they given to us at birth, and we, so to speak,
[00:18:45] try to preserve them in ourselves? This is
[00:18:48] a very good question, to which it's not so easy to give
[00:18:52] an answer, because as I already said, our different tissues and
[00:18:55] organs renew at different rates, so in some
[00:18:59] tissues the set of stem cells is activated quite
[00:19:02] often, for example, well, in the same skin there are at least five
[00:19:06] or six types... there is a hair follicle
[00:19:16] next to it, there is its own subtype of stem cells, they
[00:19:19] work quite often and actively, because
[00:19:23] the skin renews actively, the same can be said about stem cells
[00:19:27] of the intestine, the intestinal mucosa renews quite
[00:19:30] actively, yes, therefore stem cells there, well, so to speak,
[00:19:34] work often, at the same time... in many
[00:19:38] other organs tissues there can be
[00:19:41] silent stem cells, and it is generally believed that a stem cell by
[00:19:44] definition should be at rest and its environment
[00:19:48] ensures this rest, only in case of damage it
[00:19:51] should activate, begin to divide, begin
[00:19:55] this process of specialization, differentiation.
[00:19:58] There were interesting studies when in very long-
[00:20:02] lived people, centenarians, that is, people living over 100 years old,
[00:20:05] they studied through complex molecular
[00:20:07] genetic analysis how many stem cells in the bone marrow
[00:20:11] activated to give rise to blood cells, these are hematopoietic
[00:20:15] stem cells, which differentiating
[00:20:18] give erythrocytes, leukocytes, yes,
[00:20:21] megakaryocytes and platelets in them, these
[00:20:24] cells, as it turned out, in a woman, if I'm not mistaken,
[00:20:27] 114 years of life, activated only a few, that is, the
[00:20:31] progenitors of all her blood cells throughout her life were
[00:20:35] only a few, a very interesting story:
[00:20:37] but how this happens in other tissues, this is a very
[00:20:40] difficult research question, we also have a third
[00:20:44] mechanism, which was discovered relatively recently,
[00:20:48] already in the 21st century, many researchers began
[00:20:51] to talk and write about it, this is the mechanism of transdifferentiation,
[00:20:55] the transformation of one type of mature cells
[00:20:58] into another, while, of course, it is necessary to seriously
[00:21:02] reorganize, and return from the point of view of implementing the genetic
[00:21:06] program, such a more undifferentiated, more
[00:21:09] unspecialized state, now many researchers
[00:21:13] are engaged in the question of how close this intermediate
[00:21:16] state is to a stem cell during transdifferentiation,
[00:21:20] or there are mechanisms of transition, change of phenotype
[00:21:24] of one cell type to another, which is now
[00:21:28] more needed by this tissue, that is, at some
[00:21:31] moments ordinary cells, for example, skin cells
[00:21:35] under the influence of some circumstances
[00:21:37] can become bone cells, rather, this process is
[00:21:41] well described when skin cells, epithelial
[00:21:45] cells, turn into cells more similar to connective
[00:21:48] tissue cells, because they are better, then they can move towards
[00:21:52] the damage and replace
[00:21:55] the defect that has arisen, and this happens without the involvement
[00:21:58] of stem cells, one specialized cell
[00:22:01] turned into another type and function cell.
[00:22:05] There is such a graph when I show that an excess of fatty tissue
[00:22:09] and a lack are absolutely equally
[00:22:11] unacceptable. We know that fatty tissue is a factory for
[00:22:15] producing a huge amount of all sorts of vital substances, but is this
[00:22:19] history not also connected with the fact that fatty tissue is a great
[00:22:22] source of stem cells? This is a wonderful
[00:22:26] example when the idea of stem cells, yes,
[00:22:29] is formed on the basis of some kind of, do not
[00:22:32] be offended, only a layman's understanding of cell therapy, why do you
[00:22:36] talk about fatty tissue? Well, surely, because you read in many
[00:22:39] publications that for cell therapy, for regenerative medicine,
[00:22:42] fatty tissue cells were used, but they were used not because
[00:22:45] there are so many of them or they are somehow special, but simply
[00:22:49] because.
[00:23:05] used for regenerative medicine
[00:23:08] as a drug, yes, as a therapeutic agent, and they are somehow
[00:23:11] associated with the wall of blood
[00:23:15] vessels, respectively, in a well-vascularized tissue, there are more of them per gram
[00:23:18] of tissue yield. This is the only reason why
[00:23:22] fatty tissue is very often used, while
[00:23:26] it is well known that in all, in
[00:23:29] all tissues there are these subpopulations, that
[00:23:33] is, a small number of stem cells, which we call tissue-
[00:23:36] specific, yes, that is, they are intended for the restoration
[00:23:39] of this particular tissue, and perhaps I will allow myself such
[00:23:42] a generalization, if there is an opportunity in a direct
[00:23:46] comparative experiment to use one's own
[00:23:49] non-specific cells, uh-huh, cells of the
[00:23:52] same fatty tissue or bone marrow, which are also quite
[00:23:56] easy to obtain, then usually tissue-specific cells are better,
[00:24:00] but isolating them and making medicine from them is very often
[00:24:03] not easy, especially if it is some
[00:24:06] hard-to-reach organ from which you can't just take a biopsy, right?
[00:24:10] Well, of course, then they take instead
[00:24:13] more easily accessible sources for cell
[00:24:17] therapy.
[00:24:21] here somewhere they are actively printing thoughts about how soon
[00:24:25] you won't have to deal with teeth at all, because
[00:24:28] don't throw them away,
[00:24:31] they say, from them they will extract stem cells
[00:24:35] and then replace your whole jaw, yes, like a
[00:24:39] garden, is this fantasy or can we
[00:24:42] already prepare? It's true, teeth,
[00:24:45] especially good healthy teeth
[00:24:47] without damage. which are
[00:24:50] removed, for example, sometimes even in adults, wisdom teeth are removed
[00:24:54] due to their incorrect
[00:24:56] position, and I won't even mention baby teeth, they are an excellent
[00:25:00] source of stem cells, they are called stem
[00:25:03] cells of the pulp, or stem cells are also isolated
[00:25:07] from the ligaments surrounding the teeth, they have
[00:25:10] a specific origin during embryogenesis, they
[00:25:14] have a slightly different origin than many stem cells of other
[00:25:17] organs, they have an advantage in
[00:25:21] how they can divide, that is, build up, yes,
[00:25:24] similar ones for cell therapy, and there are some
[00:25:27] advantages in terms of the ability to specialize in a certain tissue,
[00:25:31] for example, in bone, cells from the pulp
[00:25:34] of a tooth are an excellent source for restoring
[00:25:37] hard bone-like tissues, including for
[00:25:41] jaws, for example, or even for long tubular bones, they are very
[00:25:45] actively used, so yes, it is a very good source, the only thing is that they
[00:25:49] need to be very, very quickly brought to a laboratory that
[00:25:52] powerful cells. Well, how to store baby teeth for
[00:25:55] the future, or is it just
[00:25:58] that you need to find a partner, a place where
[00:26:02] your wonderful stem cells can be isolated and preserved,
[00:26:05] and this is already a question concerning proper biobanking
[00:26:09] of cell collections, this is a separate very interesting field,
[00:26:12] closely related to regenerative medicine, because
[00:26:16] without proper preservation of cell
[00:26:19] lines, cell populations, the development
[00:26:22] of our field is difficult to imagine, therefore
[00:26:25] specialized laboratories and specialized
[00:26:28] banks, biobanks, are needed where such material can be processed.
[00:26:34] Look, what our listeners will hear: now
[00:26:37] we go to the dentist, immediately extract teeth, look for
[00:26:41] a laboratory that will preserve them for us, so that later, yes,
[00:26:45] but this is not streamlined, a person cannot
[00:26:48] just come and store these teeth, it's also pointless to store these
[00:26:52] teeth now, so this is, let's say, a perspective
[00:26:56] for some time, someday, just like now we go to the laboratory, donate blood,
[00:27:00] someday a person will say: tomorrow I'm going to have a wisdom tooth extracted,
[00:27:03] please, I don't know, give me
[00:27:07] a container in which I will bring the tooth to you
[00:27:10] and you will then preserve my cellular
[00:27:13] material, it's the same as with umbilical cord blood cells, yes,
[00:27:17] I believe that we can absolutely calmly talk about
[00:27:20] preserving cells from the pulp as also a kind of biological
[00:27:23] insurance, it's just that now, unfortunately, in our country, as you rightly say, it's not
[00:27:27] streamlined, I think it's not streamlined in the
[00:27:30] world either.
[00:27:32] Not in the world either, yes, well, let's say, I, I don't know,
[00:27:36] froze teeth
[00:27:39] or something else, can
[00:27:42] I give my biological material to
[00:27:46] another person who needs it more,
[00:27:49] or will it not work like that? Let's
[00:27:53] break your question down into two components. The first component
[00:27:56] is bioethical, uh-huh, if you are responsible for yourself, if you
[00:28:00] give voluntary informed consent?
[00:28:13] from one person for the treatment of another person's disease, this is an absolutely correct and normal
[00:28:16] story, in fact cell therapy is divided
[00:28:20] into autologous, when a patient can be treated with
[00:28:23] his own cells and products created from his own
[00:28:26] cells, or allogeneic, when he receives cells
[00:28:30] from donors, in fact examples of allogeneic...
[00:28:40] you 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
[00:28:43] medical, scientifically based application of stem cells for
[00:28:46] tissue regeneration, well, in this situation,
[00:28:50] yes, allogeneic autologous cell
[00:28:54] therapy is justified in certain cases and has its own
[00:28:57] advantages and disadvantages, well, if briefly, autologous therapy
[00:29:00] is undoubtedly this...
[00:29:32] since functional capabilities, this very regenerative potential, this is
[00:29:36] shown in a very large number of studies, it worsens,
[00:29:39] then treatment with one's own cells can be much
[00:29:43] less effective than it was shown and assumed in an experiment, for example.
[00:29:46] In this sense, allogeneic therapy may
[00:29:50] be more advantageous, that is, cells from a young,
[00:29:53] relatively healthy donor who has given his consent can be
[00:29:57] used in this case. In addition, allogeneic therapy has another
[00:30:00] significant advantage. You can produce this
[00:30:04] product in advance, check its safety, quality, its
[00:30:08] effectiveness, and then, when the patient comes, you can
[00:30:11] request this product from the bank and use it as
[00:30:15] prescribed, and for many clinical
[00:30:18] tasks, the time required to prepare
[00:30:21] the product can be a significant factor, so
[00:30:25] it can be used if there are indications.
[00:30:28] Did I hear correctly that in the treatment of
[00:30:31] oncology: cell therapy is now used, moreover,
[00:30:35] I would say that it is in the treatment of oncology, first of all, like
[00:30:38] hematological diseases, we are now seeing just a
[00:30:42] boom in new products, yes
[00:30:45] and then we go in the direction of autoimmune
[00:30:48] diseases, and here I wanted to ask, there are many
[00:30:52] interesting promising targets related to the fact that cells
[00:30:55] regulate the immune system's response to
[00:30:59] the emergence of foreign antigens, native cells, or when
[00:31:03] the immune system for some reason starts to react against its own cells,
[00:31:07] here the prospects for cell therapy are very great, it's
[00:31:10] not quite regenerative medicine, yes, it's more like
[00:31:14] cells. smart killers, however, as a
[00:31:17] therapeutic agent, as a medicine, these are living cells, and not
[00:31:21] just living cells, but also genetically modified
[00:31:24] in order to better recognize
[00:31:28] a tumor cell, these cells are
[00:31:31] from, as it turns out, well, that is, from the cancer
[00:31:35] patient himself, yes, they are suitable, they are suitable, yes, if
[00:31:39] you teach them in the right way, they are suitable,
[00:31:43] in our field.
[00:31:45] in such regenerative medicine, specifically aimed at
[00:31:48] controlling tissue regeneration processes,
[00:31:52] our medicine, it seems to me, is wonderful because we are not
[00:31:56] limited by any clinical direction, the
[00:31:59] mechanisms we are dealing with are universal for different organs
[00:32:02] and tissues, and can be applied to a very wide range of
[00:32:05] clinical tasks, well,
[00:32:08] I like to talk about our very
[00:32:11] valuable project for Moscow University.
[00:32:15] when from a fundamental idea, from a
[00:32:18] project to study stem cells and their functioning
[00:32:22] in tissues, I must say that this is a very
[00:32:25] difficult story, because we talked a lot about how
[00:32:29] unique properties stem cells must have, who ensures
[00:32:32] their preservation of these unique conditions in
[00:32:35] tissues, a special microenvironment, it is called
[00:32:39] the stem cell niche, so the existence of this niche
[00:32:43] in different tissues and organs. and regulation, very complex
[00:32:47] regulation between the components of this niche, this is a subject for
[00:32:50] fundamental study, so
[00:32:53] at the Center for Regenerative Medicine of Moscow State University, we are engaged in
[00:32:56] issues of just regulating lower stem cells, as a
[00:33:00] model we used the niche of spermatogonial stem cells, do not
[00:33:03] try to repeat a very complex term, but these are the stem
[00:33:07] cells that work to produce spermatozoa,
[00:33:10] ensuring the reproductive function of men, in case of damage
[00:33:14] like this... a block of spermatogenesis occurs and fertility
[00:33:17] is impaired, now this is a very, very serious problem,
[00:33:21] so we model such disorders of
[00:33:24] spermatogenesis in animals using various influences, look how
[00:33:27] small and atrophied the testis can be when damaged and
[00:33:31] how much the structure of the seminiferous tubules is disrupted,
[00:33:35] literally the production of specialized cells from stem cells is blocked,
[00:33:38] the testicle becomes so small when damaged, this is due to
[00:33:42] the fact that a - a block occurs at the tissue
[00:33:45] level, literally a block of the process of formation of
[00:33:49] differentiated spermatozoa
[00:33:52] from stem cells, and we showed that if on
[00:33:56] such models of damage we try to
[00:33:59] restore the niche normal microenvironment
[00:34:03] of cells, and we did this by introducing
[00:34:06] mesenchymal stromal stem cells into the testis
[00:34:08] itself, or not cells, but those biologically active factors
[00:34:12] that they secrete, we called them a secret, right?
[00:34:24] Below is a slide showing that even the mass of the testes recovers after a few months, and so does the function,
[00:34:28] remembering the tasks of regenerative medicine, the function is realized in
[00:34:31] the form of production of spermatozoa from stem cells, and not
[00:34:35] just spermatozoa, but motile ones, those that ensure fertility,
[00:34:39] in animals we see partial restoration of the ability to give
[00:34:42] healthy, normal offspring in men. You are great, you
[00:34:46] save girls,
[00:34:49] for girls it’s a bit different, yes, the situation is arranged,
[00:34:52] if in men these stem cells work throughout their lives to
[00:34:56] produce specialized cells, then in women, as you
[00:34:59] know, they are laid down at birth, then only gradually
[00:35:03] come out, are used, so there it turns out to be a somewhat
[00:35:07] fundamentally different story with the impact on stem cells,
[00:35:11] and this is not translated mechanistically, although of course we actively. regulation
[00:35:19] of this process also, that is, egg cells
[00:35:22] cells at all,
[00:35:25] it's more complicated, as I understand it, this is a slightly more complex
[00:35:28] story, although of course scientists are also actively working on it,
[00:35:31] this is primarily related to the possibility of
[00:35:35] controlling what is called the potency of stem
[00:35:38] cells, when we talked with you about the ability to
[00:35:41] differentiate, it actually differs in different types. of the body,
[00:35:53] their potency is reduced, it's clear why, because we don't need our
[00:35:57] cells to turn into anything under the influence of some
[00:36:01] sudden chaotic factors, but when it's
[00:36:04] an embryo, and even more so, when it's...