History of stem cell research
The discovery of stem cells was one of the most important achievements in biology and medicine. This section explores key moments and achievements in the history of stem cell research.
The Discovery of Stem Cells - Alexander Maksimov
Cambial tissues - Alexey Zavarzin
Bone marrow transplantation - Georges Mate (France).
Discovery of mesenchymal stem cells (MSCs) - Aleksandr Friedenstein
Research of MSC and HSC - Joseph Chertkov
The beginning of widespread Use of MSCs - Anatoly Konoplyannikov
Isolation of embryonic stem cells - James Thomson
Isolation of MSCs from fat cells- Mark Hedrick
Opening of a center in Moscow for treatment with donor bone marrow stem cells. - Valery Tychinin
Nobel Prize - John Gordon
Nobel Prize - Shinya Yamanaka
Dokar Vita Cells
Stages of MSC production
Contacts
Discovery of stem cells
Aleksandr Maximov, 1909
Aleksandr Aleksandrovich Maximov (Russia)
(January 22 (February 3), 1874, St. Petersburg – December 4, 1928, Chicago) – Russian and American scientist – histologist and embryologist, Corresponding Member of the Russian Academy of Sciences, professor at the University of Chicago.
The term "stem cell," as we use it today, was first introduced on June 1, 1909, at a meeting of the Hematology Society in Berlin. At the meeting, Aleksandr Aleksandrovich Maximov presented a paper in which he described cells capable of giving rise to other cell types, or, in other words, the essence of hematopoiesis—the transformation of hematopoietic stem cells into various blood cells.
"I have now discovered that these primitive blood cells, as I call them, are in no way erythroblasts, as would be expected from the generally accepted view, but rather completely undifferentiated elements with a round, light nucleus and narrow, basophilic protoplasm; "They are neither red nor white blood cells, although they could probably be called white blood cells, since they sometimes, especially in chickens, have an amoeboid shape and are very similar to large lymphocytes," Aleksandr Maximov reported in his report (as it turns out, he wasn't entirely correct).
This presentation was preceded by long, painstaking work studying hematopoiesis. His research into cellular changes during inflammation was only the beginning. Maximov, among other things, traveled to marine stations, where he collected the necessary biomaterial. His laboratory contained hundreds of slides containing tissue sections for histological experiments.

The scientist described variations of the hematopoiesis process, literally depicting it in diagrams, in which stem cells rightfully occupied their place.

These drawings are housed in the library of the University of Chicago, where Maximov worked in exile. Alexander Alexandrovich simultaneously studied the development of blood elements and hematopoietic organs in the embryo and attempted to describe and classify blood cells and connective tissue. Thus, gradually, year after year, he gained evidence for his concept, which he presented in Berlin. According to his conclusion, blood cells develop from stem cells. Such a cell divides, self-renews, and transforms into other cell types, resembling a tree trunk from which develop leaves and branches—blood and tissue cells.
The ideas expressed by Maximov at the Berlin meeting of the Society of Hematologists were significantly ahead of their time. They were not readily accepted. Although by that time, Alexander Alexandrovich had already headed the Department of Histology and Embryology at his native academy in Russia for several years and his name had become well-known in international scientific circles, the scientific community reacted to his presentation with caution and even skepticism. Maksimov's assertion that hematopoietic stem cell differentiation occurs as a result of local influences generated by the bone marrow stroma, which forms the microenvironment for hematopoietic cells, was met with disbelief. This is now a confirmed fact. Another of his theories, which raised doubts, concerned the origin of what are now called multipotent mesenchymal stromal cells, which are capable of differentiating into bone, fat, and cartilage cells. Confirmation of the scientist's assertions has now been found: it has been experimentally proven that these cells are formed from the tissue that forms that very microenvironment. All of this ultimately has implications for bone marrow transplantation, for a better understanding of how donor cells seed the recipient's bone marrow, and so on.

True to His Calling
In 1914, in St. Petersburg, Aleksandr Aleksandrovich published the textbook "Fundamentals of Histology," which, according to him, consisted of a systematic and somewhat enriched collection of lectures he had given to first- and second-year students at the Imperial Military Medical Academy over the course of ten years. The textbook included illustrations by the scientist himself, and it became a true reference for medical students.
In 1918, his colleagues nominated Aleksndr Maximov for the Nobel Prize in Medicine or Physiology, honoring his scientific work. But nothing further was forthcoming. Events at the time were not favorable. A year later, Maximov became a professor at Petrograd University, although many opposed his appointment. Opportunities for full-time scientific work were dwindling.
As a result, after three years, he was forced to give up everything. Together with his wife, stepson, and older sister, Maximov crossed the border across the frozen Gulf of Finland and left the country. They reached the United States. Aleksandr Aleksandrovich spent the last six years of his life in America (hence his frequent description as a Russian-American scientist), working at the University of Chicago, where he continued histological research.
The name of Aleksandr Aleksandrovich Maximov was long banned in the Soviet Union. However, his textbook on histology went through dozens of editions and is still considered one of the best in this field of medicine.

Cambium
Alexey Zavarzin, 1909
Alexey Alekseevich Zavarzin (USSR)
(1886–1945) – Soviet histologist, first director of the Institute of Biological Sciences of the Perm National Research Polytechnic University, the USSR Academy of Sciences and the USSR Academy of Medical Sciences, major general of the medical service, founder of evolutionary histology.
In 1932, in his textbook, "A Course in General Histology," Professor A. A. Zavarzin argued for a close connection between blood and connective tissue as a single environment within the body, with undifferentiated cells, which Zavarzin called hematopoietic mesenchymal cells. They give rise to poorly differentiated cells, ultimately differentiated cells. These cells are not called stem cells, although it is clear that this is precisely the dominance of the system, according to the hypothesis. A. A. Zavarzin used the concept of cambium. Cambial tissues "preserve the germinal material obtained from embryonic embryos throughout life," that is, a reserve of undifferentiated elements (cambium), which can be replenished when the number of differentiated elements decreases. Zavarzin also emphasized that cambial cells do not remain unchanged during different periods of human ontogenesis.
The first bone marrow transplant
Georges Mate, 1958
Georges Mate (France)
(1922–2010) — A French oncologist and immunologist. He performed the world's first bone marrow transplant between unrelated donors and hosts.
  • In November 1958, he performed the world's first bone marrow transplant between unrelated donors and hosts to save six Yugoslav nuclear researchers who had been accidentally irradiated.
  • In 1961, he became head of the hematology department at the Gustave Roussy Institute in Villejuif.
  • In 1964, he founded the Institute of Oncology and Immunogenetics, where he created the first sterile hospital wards.
  • From 1966 to 1990, he taught experimental oncology at the University of Paris.
  • From 1980 to 1988, he founded and directed the Blood Diseases and Tumors Service at Paul-Brousse Hospital.
  • He was one of the co-founders of the European Group for Anti-Cancer Chemotherapy (G.E.C.A.).
  • From 1990 to 2008 he worked as a consultant at the Paris Swiss Hospital, the Rome European Hospital, the Sofia Oncology Hospital, the Belgrade Civil Hospital and the Paul-Brousse Hospital.
Discovery of mesenchymal stem cells
Alexander Friedenstein, 1972
Aleksandr Yakovlevich Friedenstein (USSR)
Aleksandr Yakovlevich Friedenstein (June 24, 1924, Kyiv – August 31, 1997, Moscow) was a Soviet medical scientist, histologist, hematologist, and immunologist. Corresponding Member of the USSR Academy of Medical Sciences (1991) and the Russian Academy of Medical Sciences (1992).
He was the first to describe and experimentally confirm the existence of stromal stem cells, later internationally known as multipotent mesenchymal stromal cells (MSCs), in bone marrow and lymphoid organs.
A. Ya. Friedenstein's scientific career began in the turbulent climate of post-war Europe, where his formative years were characterized by an insatiable curiosity about the complexities of biological phenomena. Beginning with experiments on amphibian tissue regeneration and culminating in his years as a graduate student under the renowned histologist A.V. Rumyantsev, A. Ya. Friedenstein honed his analytical acumen and experimental skills in the crucible of histological research. It was during this period that his fascination with stem cells first awakened. He clearly recognized the regenerative potential inherent in the tissue microenvironment and began searching for ways to decipher the mechanisms underlying it. In 1950, the experimental results were presented as a PhD dissertation, "Histogenesis of the Visceral Skeleton of Higher Vertebrates."

A. Ya. Friedenstein was the first to identify two categories of osteogenic progenitor cells: determined (DOPC) and induced (IPC). This hypothesis was later confirmed experimentally. His monograph, "Bone Tissue Induction and Osteogenesis," published in 1973, contained the most comprehensive and detailed analysis of his experimental data. After successfully defending his doctoral dissertation, "Histogenetic Analysis of Extraskeletal Osteogenesis," in 1963, A. Ya. Friedenstein headed the Immunomorphology Laboratory and led it for over 25 years. In 1967, he was awarded the title of professor, and in 1987, A. Ya. Friedenstein was elected a Corresponding Member of the USSR Academy of Medical Sciences.
For over 30 years, Alexander Yakovlevich taught immunomorphology at the Department of Cytology and Histology in the Biology Faculty of Moscow State University. A leading expert in immunology, he actively participated in the founding and work of the "Immunologists' Club," organized at the Gamaleya Research Institute of Epidemiology and Microbiology by Academician O.V. Baroyan.
During this period, Alexander Yakovlevich developed a particular interest in the work of the leading histologist A.A. Maksimov, conducted in the early 20th century. Analyzing his work and comparing it with the results obtained in his own and other laboratories, he identified a strong interest in stem cell issues.
Since the early 1960s, the research of A.Ya. Friedenstein and his colleagues has been devoted to the study of stromal cells of hematopoietic and lymphoid tissues. It was shown that heterotopic transplantation of bone marrow or lymphoid organ fragments results in the formation of a bone marrow or lymphoid organ, respectively, at the transplant site, and that the de novo structures formed are chimeric: the hematopoietic and lymphoid tissue belongs to the recipient, while the stromal tissue belongs to the donor. These pioneering studies demonstrated the existence of a stromal cell lineage, histogenetically independent of hematopoietic cells, that carries a specific microenvironment that facilitates the proliferation and differentiation of hematopoietic and lymphoid cells.
The answer to the question of which stromal cells are responsible for the transfer and organization of a specific hematopoietic or lymphoid microenvironment was obtained through a selective cloning method developed in the Immunomorphology Laboratory. This method was used for the first time to isolate a unique category of clonogenic stromal progenitor cells, the properties of which determine the main characteristics of the microenvironment. Subsequent studies of monoclonal strains of these cells revealed that they include a category of cells that possess high proliferative potential, self-sustain during proliferation, and differentiate in several directions (bone, cartilage, connective tissue, and adipose tissue). These cells fully meet the requirements for stem cells and are considered bone marrow stromal stem cells.
A distinctive feature of A. Ya. Friedenstein's scientific legacy is his pioneering research into the properties and functions of stromal stem cells in hematopoietic and lymphoid tissues. Building on the foundation laid by his predecessors, A. Ya. A. Ya. Friedenstein conducted a series of groundbreaking experiments that revealed the histogenetic independence of stromal cells from hematopoietic lineages and defined their key role in the formation of a tissue-specific microenvironment. Using a combination of heterotopic transplantation models and selective cloning methods, A. Ya. Friedenstein and his colleagues elucidated the complex system of intercellular interactions that underlie hematopoietic and lymphoid homeostasis and uncovered the fundamental principles governing tissue morphogenesis and regeneration.
In the mid-1980s, A. Ya. Friedenstein conducted numerous studies abroad. Together with M. Owen (Oxford, England), he conducted research on osteogenic cell markers and differentiation, and with R. Robby (Bethesda, USA), he studied the influence of certain growth factors on the cloning of bone marrow stromal stem cells.
The Scientific Legacy of A. Ya. A. Ya. Friedenstein's work extends beyond basic research, as his discoveries have profound implications for regenerative medicine and therapeutic intervention. Through international collaborations and interdisciplinary partnerships, A. Ya. Friedenstein led efforts to translate laboratory research findings into practical therapeutic approaches, catalyzing a renaissance in regenerative medicine and laying the foundation for future breakthroughs in tissue engineering and cell therapy.
With a distinguished scientific legacy, Alexander Yakovlevich Friedenstein left an indelible mark on the annals of immunomorphology, inspiring subsequent generations of researchers to push the boundaries of knowledge and explore the possibilities of regenerative medicine. His unwavering commitment to scientific research, combined with visionary leadership and scientific insight, serve as an inspiration to both aspiring scientists and seasoned practitioners. Reflecting on the colossal contributions of A. Ya. Friedenstein's contributions to stem cell biology and tissue regeneration research remind us of the enduring power of scientific curiosity, which can illuminate the darkest corners of the unknown and pave new paths to a brighter, healthier future for all humanity.
Study of MSCs and HSCs
Iosif Chertkov, 1980
Chertkov Iosif Lvovich (USSR)
Iosif Lvovich Chertkov (1927–2009) was a prominent Soviet and Russian experimental hematologist, Doctor of Medical Sciences, and professor.
Key biographical details:
  • Author of 7 monographs and over 300 scientific papers.
  • Co-author of more than 20 patents.
  • Key monographs:
  • "Cellular Foundations of Immunity" (1969, co-authored with A. Ya. Friedenstein);
  • "Cellular Foundations of Hematopoiesis" (1977, co-authored);
  • "The Hematopoietic Stem Cell and Its Microenvironment" (1984, co-authored with O. A. Gurevich) — a fundamental reference work for hematologists.
  • He established a laboratory for the physiology of hematopoiesis.
  • Beginning in the mid-1970s, he—together with A. Y. Friedenstein—laid the foundation for the experimental study of bone marrow stem cells.
Chertkov Iosif Lvovich – an eminent experimental hematologist, Doctor of Medical Sciences, professor, and chief researcher at the Hematology Research Center of the Russian Academy of Medical Sciences (RAMN).
Iosif Lvovich Chertkov was born in 1927 in the city of Odessa. In 1947, he graduated from the Faculty of General Medicine at the First Moscow Medical Institute. From 1956, he worked at the Hematology Research Center of the RAMN—initially as a senior researcher, then as a laboratory head (until 1996), and from 1997 onward, as a chief researcher.
I. L. Chertkov made a significant contribution to the study of the clonality of hematopoiesis. He established that hematopoietic stem cells (HSCs) possess a high, yet finite, proliferative potential; they are not immortal and cannot "self-sustain" indefinitely. HSCs are established solely during embryogenesis and are consumed progressively, giving rise to a succession of short-lived, localized cell clones—a process analogous to what occurs in the ovary.
Iosif Lvovich also demonstrated that mesenchymal stem cells (MSCs)—the progenitors of the hematopoietic microenvironment—differ from HSCs in terms of radiosensitivity. When bone marrow is transplanted intravenously as a single-cell suspension, MSCs are lost; they are unable to reach the specific micro-niches where they function, even if the bone marrow suspension is injected directly into the bone. MSCs can only successfully transfer the hematopoietic microenvironment when transplanted—for instance, under the skin or beneath the renal capsule—without the bone marrow being processed into a single-cell suspension.
In his work, Chertkov was the first to establish the physiological characteristics of mesenchymal stem cells (MSCs) and obtain fundamental data on the clonal kinetics of hematopoietic stem cells (HSCs). These findings have since been corroborated by the global scientific community. It has been demonstrated that donor MSCs do not survive following intravenous bone marrow transplantation; furthermore, clones of "healthy" HSCs have been identified in patients with hematoproliferative disorders. The insights into the clonality of hematopoiesis were also confirmed through research conducted in the aftermath of the Chernobyl disaster.
Beginning in the mid-1970s, I. L. Chertkov, in collaboration with A. Y. Friedenstein, laid the groundwork for the experimental study of bone marrow stem cells. Chertkov focused on two types of stem cells—hematopoietic and mesenchymal—and in 1984, he published a monograph titled *The Hematopoietic Stem Cell and Its Microenvironment*, which remains a key reference for hematologists to this day.
Moreover, Iosif Lvovich was a pioneer in hybridoma technology; he founded the first company in the USSR to produce monoclonal antibodies. Several diagnostic agents based on monoclonal antibodies—developed by Chertkov for blood-type determination—remain in widespread use today.
I. L. Chertkov authored a series of pioneering studies on "Hematopoietic and Mesenchymal Stem Cells"; in total, he published 4 monographs and over 300 articles in both domestic and international journals.
Practical application of MSCs
Anatoly Konoplyannikov, 1988
Anatoly Georgiyevich Konoplyannikov (Russia)
Professor

Doctor of Biological Sciences, Head of the Department of Cellular and Experimental Radiation Therapy at the National Medical Research Radiological Centre (NMRRC) of the Ministry of Health of the Russian Federation.

  • Over 700 scientific publications
  • More than 10 monographs
  • Author or co-author of 20 patents for inventions
  • Pioneered the use of mesenchymal stem cell transplantation
  • Established a stem cell bank
  • Recipient of the Russian Government Prize in Science and Technology
  • Honored Scientist of the Russian Federation
  • Member of the Gerontological Society of the Russian Academy of Sciences (RAS)
  • Member of the National Society for Regenerative Medicine
  • Member of the International Society for Stem Cell Research (ISSCR)
Recipient of the Russian Federation Government Prize in Science and Technology (1998), full member of the ISSCR (International Society for Stem Cell Research), and head of the Scientific Council at the R&D enterprise "Innovative Cellular Technologies."
In 1960, he graduated from the Faculty of General Medicine at the Stavropol Medical Institute. From 1962 to 1965, he pursued postgraduate studies at the Institute of Medical Radiology of the Russian Academy of Medical Sciences (RAMS). His career path progressed from postgraduate student, assistant, and associate professor to head of a department.
He defended his Candidate of Sciences dissertation in 1966 and his doctoral dissertation in 1978.
He is the author of over 500 scientific publications and holds or co-holds 20 patents for inventions.
His scientific interests include radiotherapy in oncology, the transplantation of mesenchymal stem cells, and the organization of stem cell banks.
In 1966, A. G. Konoplyannikov successfully defended his Candidate of Sciences dissertation, titled "Certain Aspects of the Biological Effects of Ionizing Radiation with Varying Linear Energy Transfer (LET) Values," before the Academic Council of the Faculty of Biology and Soil Science at Moscow State University (MSU). Following his postgraduate studies—and continuing until October 2019—he worked at the Institute of Medical Radiology (now the Medical Radiological Research Center of the RAMS). His roles included junior researcher in the Department of Biophysics (within the institute’s experimental sector), senior researcher, and subsequently head of the Laboratory of Experimental Radiation Therapy, as well as head of the Department of Cellular and Experimental Radiation Therapy (within the institute’s clinical sector). In 1980, A. G. Konoplyannikov defended his doctoral dissertation, titled "Quantitative Patterns of Radiation-Induced Damage, Protection, and Recovery in Normal and Tumor Cells within an Animal Organism," earning the degree of Doctor of Biological Sciences. In 1986, he was awarded the title of professor in the field of radiobiology; in 1998, he received the Russian Government Prize in Science and Technology; and in 2014, he was named an Honored Scientist of the Russian Federation. Anatoly Georgievich was a member of the Gerontological Society of the Russian Academy of Sciences and the National Society for Regenerative Medicine, and, from 2008, a member of the International Society for Stem Cell Research (ISSCR).
Anatoly Georgievich authored over 700 scientific publications, more than a dozen monographs (both individual and co-authored), and held over 20 patents for inventions. Under his supervision, 21 candidates of sciences (PhD-equivalent) and 7 doctors of sciences (higher doctoral degree) successfully defended their dissertations.
A unique aspect of Anatoly Georgievich’s scientific work was his success in translating experimental research findings into clinical practice.
A. G. Konoplyannikov’s research interests were exceptionally broad, encompassing fields such as regenerative medicine; the systemic transplantation of autologous and allogeneic multipotent mesenchymal stromal cells derived from bone marrow for the treatment of various diseases; stem cells of the intestinal epithelium and "spermatogenic epithelium"; cancer stem cells; nanotheranostics; radiation therapy for cancer patients (including combinations with hyperthermia, electron-affinic compounds, or immunotherapy); the study of nitric oxide production and metabolism in the blood and tissues of laboratory animals; the effects of electromagnetic fields and microwave hyperthermia; and the radiobiology of non-ionizing radiation.
He maintained extensive scientific collaborations—not only within his own institute but also across various cities in Russia and the former Soviet republics, as well as internationally (including in the United States, the Czech Republic, Germany, and Hungary).
Isolation of human embryonic stem cells.
James Alexander Thomson, 1998
James Alexander Thomson, USA
Professor

An American biologist whose research in the field of stem cells represented a major scientific breakthrough. He is known for two key achievements: the first isolation of human embryonic stem cell lines and the creation of induced pluripotent stem cells (iPS cells).

  • Thomson is a member of the National Academy of Sciences and a recipient of numerous prizes and awards.
  • In 1999, Thomson received the Golden Plate Award from the American Academy of Achievement.
  • In 2001, he was featured on the cover of TIME magazine in a segment titled "America's Best in Science & Medicine" for his work with human embryonic stem cells; he appeared again in 2008, when the magazine named him one of the 100 most influential people in the world for his development of human induced pluripotent stem cells.
  • In 2011, Thomson—along with Dr. Shinya Yamanaka—was a recipient of the King Faisal International Prize and the Albany Medical Center Prize.
  • In 2013, Thomson received an honorary Doctor of Science degree from the University of Illinois at Urbana-Champaign.
  • He also received the McEwen Award for Innovation from the International Society for Stem Cell Research in 2013.
Embryonic stem cell research
In 1995, Thomson became the first person in the world to successfully isolate and culture embryonic stem cells from a non-human primate—the rhesus macaque. This achievement laid the foundation for subsequent work with human embryonic stem cells.
In 1998, his laboratory was the first to report the successful isolation of human embryonic stem cells. The study’s findings were published in the journal *Science* on November 6, 1998, under the title "Embryonic Stem Cell Lines Derived from Human Blastocysts." Thomson and his team derived five stem cell lines from the blastocysts of five different embryos. This discovery sparked widespread ethical debate, as the process of obtaining such cells required the destruction of an embryo.
In 1999, the journal *Science* named the discovery of embryonic stem cells the "Breakthrough of the Year."

Induced pluripotent stem cells (iPS cells)
In 2007, Thomson’s group (concurrently with researchers led by Shinya Yamanaka) reported a method for converting human skin cells into cells that closely resemble embryonic stem cells. These cells were termed induced pluripotent stem cells (iPS cells).
This discovery had the potential to put an end to the ethical debates surrounding research involving human embryonic stem cells.

Additional facts
  • Thomson received a bachelor’s degree in biophysics from the University of Illinois (1981), as well as doctoral degrees in veterinary medicine and molecular biology from the University of Pennsylvania.
  • In 1999, he was appointed scientific director of the WiCell Research Institute, which is affiliated with the University of Wisconsin.
  • In 2008, Thomson was named director of the Regenerative Biology department at the Morgridge Institute for Research in Madison, Wisconsin.
  • His work has been recognized with numerous awards, including the King Faisal International Prize and the Albany Medical Center Prize.
  • James Thomson retired in 2022, though he has continued his scientific work.
Thomson’s research has made a significant contribution to the understanding of embryonic development processes and has opened up new possibilities for fundamental research, drug discovery, and transplant medicine.
Isolation of MSCs from adipose tissue.
Mark Hedrick , 1998
Mark Hedrick (USA)
Professor
A group of researchers led by American scientist Marc Hedrick has, for the first time, isolated stem cells from adipose (fat) tissue.
Head of the American company Cytori Therapeutics.
In 1998, a group of researchers led by American scientist Marc Hedrick succeeded in isolating stem cells from adipose (fat) tissue for the first time.
Today, many years later, mesenchymal stem cells (MSCs) are finding increasingly broad applications across various fields of medicine. Furthermore, scientists have learned to "harvest" MSCs not only from bone marrow but also from other types of tissue.
Marc Hedrick—who once headed the Laboratory of Regenerative Bioengineering within a surgery department in Los Angeles—now leads the American company Cytori Therapeutics. Having spent a long career as a plastic surgeon, he used to regret having to discard the fat removed during liposuction procedures: "I began to wonder, could it be put to some use?"
An in-depth study of adipose-derived stem cells has completely transformed my understanding of fat—it turns out that adipose tissue possesses unique properties that could be highly valuable across a wide range of medical fields! I believe it is one of the most significant types of tissue available for use. First and foremost, adipose tissue is remarkably rich in stem cells, accounting for as much as 3–5% of its composition—a far higher concentration than in any other source. For instance, 120 ml of fat can yield 5 ml of processed, high-value stem cells; that is 2,500 times more than what could be obtained from an equivalent volume of bone marrow. Furthermore, these cells do not require laboratory cultivation—they can be used immediately, in their fresh state.”
The capacity of adipose-derived stem cells to repair and regenerate areas of the body damaged by injury or disease opens up vast possibilities for applying this new technology in reconstructive surgery. “This technique is already being utilized in reconstructive surgery and for treating various types of soft and hard tissue damage; it is also beginning to be used in the treatment of diabetic foot ulcers and the restoration of damaged bone tissue,” explained Mr. Hedrick.
Opening of a center in Moscow for treatment using donor-derived bone marrow mesenchymal stromal cells (MSCs). - Valery Tychinin
Valery Tychinin, 2007
Valery Tychinin, (Russia)
In 1986 and 1987, as part of an operational task force from the USSR Ministry of Health, he participated in efforts to mitigate the consequences of the accident at the fourth reactor unit of the Chernobyl Nuclear Power Plant. For this work, he was awarded the Order of Courage (1996).
He holds the title of Honored Physician of the Russian Federation.
He is a full member of the Russian Academy of Natural Sciences (Biomedicine Section).
He served as General Director of two companies—NPO Innovative Cellular Technologies LLC and T-Helper Cellular Technologies LLC—which focused on the production of biomedical cell products based on mesenchymal stem cells. He also served as Deputy General Director for the development of regenerative medicine and cell therapy at the clinic "Stolichny Doktor" (Capital Doctor) LLC.
Since 2019, he has been a member of the Russian Society for Regenerative Medicine.
Born on June 14, 1947, in the city of Karaganda, he enrolled at the Karaganda State Medical Institute in 1965, graduating in 1972 with a medical degree specializing in hygiene and epidemiology.
Upon graduation, he was assigned to the city of Shevchenko (now Aktau, Republic of Kazakhstan) to work in Medical-Sanitary Department No. 102 of the Third Main Directorate under the USSR Ministry of Health—an organization now known as the Federal Medical-Biological Agency (FMBA) of Russia.
He served as a physician and as a department head. In 1979, he was appointed Chief State Sanitary Physician for the city of Shevchenko and the facilities of the nuclear industry—including enterprises for the extraction and processing of uranium ore, as well as the BN-350, the world’s first fast-neutron nuclear reactor.
In 1986 and 1987, as a member of an operational task force from the USSR Ministry of Health, I participated in the cleanup efforts following the accident at the fourth reactor unit of the Chernobyl Nuclear Power Plant. For this work, I was awarded the Order of Courage (1996).
In 1993, I defended my Candidate of Sciences dissertation at the Academic Council of the I. M. Sechenov First Moscow Medical Institute; the thesis was titled "Hygienic Assessment of the Integrated Use of Further-Treated Wastewater in Arid Zones."
Following the collapse of the USSR, I was transferred to Moscow in 1994, where I served until 2006 as the Chief Physician of the Head Center for State Sanitary and Epidemiological Surveillance under the Federal Medical-Biological Agency (FMBA) of Russia.
In 2003, I was awarded the title of "Honored Physician of the Russian Federation." In 2004, I was elected a full member of the Russian Academy of Natural Sciences (Biomedicine Section).
Since 2007, I have been working in the biomedical sector. I served as General Director of two companies focused on the production of biomedical cell products based on mesenchymal stem cells (MSCs)—NPO "Innovative Cell Technologies" LLC and "T-Helper Cell Technologies" LLC—and as Deputy General Director for the development of regenerative medicine and cell therapy at the "Stolichny Doktor" (Capital Doctor) clinic.
Since 2019, I have been a member of the Russian Society for Regenerative Medicine. I actively participate in conferences, symposiums, and seminars on this subject.
My work includes initiatives aimed at the professional education of physicians and public outreach regarding regenerative biomedicine, as well as the safety and efficacy of MSC-based cell therapies for various medical conditions. Since 2021, I have served as an adjunct lecturer in the Department of Cellular Biomedicine within the Faculty of Continuing Professional Education at the Pirogov Russian National Research Medical University.
Нобелевская премия - открытие клеточного репрограммирования – получения стволовых клеток из обычных.
John Gordon , 2012
John Gordon (UK)
профессор Кембриджского университета
(2 октября 1933 — 7 октября 2025) — британский биолог-эмбриолог, наиболее известный своими новаторскими исследованиями в областитрансплантации ядер и клонирования
В 2009 году он был удостоен премии Ласкера , а в 2012 году он и Синья Яманака совместно получили Нобелевскую премию по физиологии или медицине за открытие того, что зрелые клетки могут быть преобразованы в стволовые клетки .
Sir John Bertrand Gurdon
Гурдон большую часть своей исследовательской карьеры провел в Лаборатории молекулярной биологии MRC , а затем в Департаменте зоологии, где начал работать в 1972 году.  В 1983 году он стал профессором Кембриджского университета. В 1989 году он стал одним из основателей Института клеточной биологии и рака Wellcome/CRC в Кембридже, который был переименован в его честь в 2004 году, и занимал пост его председателя до 2001 года. Он был членом Совета по биоэтике Наффилда с 1991 по 1995 год, а затем магистром Магдален -колледжа в Кембридже с 1995 по 2002 год.
В 1958 году Гурдон, работавший тогда в Оксфордском университете , успешно клонировал лягушку, используя неповрежденные ядра соматических клеток головастика Xenopus . Эта работа стала важным продолжением работы Бриггса и Кинга 1952 года по трансплантации ядер из эмбриональных клеток бластулы  и успешной индукции полиплоидии у колюшки Gasterosteus aculatus в 1956 году Харом Сварупом , о которой сообщалось в журнале Nature .  В то время он не мог убедительно показать, что трансплантированные ядра происходят из полностью дифференцированной клетки . Это было окончательно доказано в 1975 году группой исследователей из Базельского института иммунологии в Швейцарии.  Они пересадили ядро ​​лимфоцита, продуцирующего антитела (доказательство его полной дифференцировки), в яйцеклетку без ядра и получили живых головастиков.
Эксперименты Гурдона привлекли внимание научного сообщества, поскольку они изменили представление о развитии, а разработанные им инструменты и методы переноса ядра используются и сегодня. Термин «клон» уже использовался с начала XX века в отношении растений. В 1963 году британский биолог Дж. Б. С. Холдейн , описывая результаты Гурдона, стал одним из первых, кто использовал слово «клон» в отношении животных.
Гурдон и его коллеги также первыми применили яйцеклетки и ооциты Xenopus (род высоководных лягушек) для трансляции микроинъецированных молекул матричной РНК, метод, который широко используется для идентификации кодируемых белков и изучения их функций.
Более поздние исследования Гурдона были сосредоточены на анализе межклеточных сигнальных факторов, участвующих в клеточной дифференциации , и на выяснении механизмов, участвующих в перепрограммировании ядра в экспериментах по трансплантации, включая роль вариантов гистонов  и деметилирование трансплантированной ДНК. 
Нобелевская премия - открытие клеточного репрограммирования – получения стволовых клеток из обычных.
Shinya Yamanaka , 2012
Shinya Yamanaka (Japan)
профессор Киотского университета
  • 2024 — Премия Research.com «Лидер в области генетики и молекулярной биологии в Японии».
  • 2012 год — Нобелевская премия за открытие того, что зрелые клетки могут быть перепрограммированы для достижения плюрипотентности.
  • 2011 г. - Член Национальной академии наук.
  • 2008 — Премия Роберта Коха
Синья Яманака работает в Киотском университете в Японии и внес значительный вклад в области биохимии, генетики и молекулярной биологии. Его исследования в основном сосредоточены на молекулярной биологии и физиологии, а также включают инфекционные заболевания, энтомологию и генетику.
Shinya Yamanaka
Синья Яманака (山中 伸弥, Yamanaka Shin'ya ; родился 4 сентября 1962 г.) — японский исследователь стволовых клеток и лауреат Нобелевской премии. Он является профессором и почетным директором Центра исследований и применения индуцированных плюрипотентных стволовых клеток (iPS-клеток ) Киотского университета; а также старшим научным сотрудником Институтов Гладстона в Сан-Франциско, штат Калифорния, связанных с Калифорнийским университетом в Сан-Франциско (UCSF) , и профессором анатомии в Калифорнийском университете в Сан-Франциско (UCSF). Яманака также является бывшим президентом Международного общества исследований стволовых клеток (ISSCR).
Он получил премию BBVA Foundation Frontiers of Knowledge Award 2010 года в категории биомедицины, премию Вольфа в области медицины 2011 года и премию Millennium Technology Prize 2012 года. В 2012 году он и Джон Гурдон были удостоены Нобелевской премии по физиологии или медицине за открытие того, что зрелые клетки могут быть преобразованы в стволовые клетки. В 2013 году он был удостоен премии Breakthrough Prize в области наук о жизни в размере 3 миллионов долларов за свою работу.
В 2006 году он и его команда получили индуцированные плюрипотентные стволовые клетки (iPS-клетки) из фибробластов взрослых мышей.  iPS-клетки очень похожи на эмбриональные стволовые клетки , in vitro эквивалент той части бластоцисты ( эмбриона через несколько дней после оплодотворения), которая развивается, чтобы стать собственно эмбрионом. Они смогли показать, что их iPS-клетки плюрипотентны , то есть способны генерировать все клеточные линии организма. Позже он и его команда получили iPS-клетки из фибробластов взрослых людей, снова став первой группой, сделавшей это. Ключевым отличием от предыдущих попыток в этой области стало использование его командой нескольких факторов транскрипции вместо трансфекции одного фактора транскрипции за эксперимент. Они начали с 24 факторов транскрипции, известных как важные на ранних стадиях развития эмбриона, но в итоге смогли сократить их количество до четырех факторов транскрипции – Sox2 , Oct4 , Klf4 и c-Myc. 
Синья Яманака обнаружил, что введение небольшого набора факторов транскрипции в дифференцированную клетку достаточно для возвращения клетки в плюрипотентное состояние. Яманака сосредоточился на факторах, важных для поддержания плюрипотентности в эмбриональных стволовых клетках (ЭСК). Это был первый случай, когда неповрежденную дифференцированную соматическую клетку удалось перепрограммировать для достижения плюрипотентности.
Зная, что факторы транскрипции участвуют в поддержании плюрипотентного состояния, он отобрал набор из 24 факторов транскрипции эмбриональных стволовых клеток в качестве кандидатов для восстановления плюрипотентности в соматических клетках. Сначала он собрал 24 фактора-кандидата. Когда все 24 гена, кодирующие эти факторы транскрипции, были введены в фибробласты кожи, лишь немногие из них действительно образовали колонии, удивительно похожие на эмбриональные стволовые клетки. Во-вторых, были проведены дальнейшие эксперименты с меньшим количеством добавленных факторов транскрипции для идентификации ключевых факторов с помощью очень простой, но чувствительной системы анализа. Наконец, он идентифицировал четыре ключевых гена. Они обнаружили, что 4 фактора транскрипции (Myc, Oct3/4, Sox2 и Klf4) были достаточны для превращения эмбриональных или взрослых фибробластов мыши в плюрипотентные стволовые клетки (способные продуцировать тератомы in vivo и участвовать в создании химерных мышей).
Эти плюрипотентные клетки называются индуцированными плюрипотентными стволовыми клетками (iPS-клетками); они встречаются с очень низкой частотой. iPS-клетки можно отобрать путем введения гена b-geo в локус Fbx15. Промотор Fbx15 активен в плюрипотентных стволовых клетках, которые индуцируют экспрессию b-geo, что, в свою очередь, приводит к устойчивости к G418; эта устойчивость помогает нам идентифицировать iPS-клетки в культуре.
Более того, в 2007 году Яманака и его коллеги обнаружили индуцированные плюрипотентные стволовые клетки (iPS-клетки) с передачей генов через зародышевую линию (путем отбора по генам Oct4 или Nanog). Также в 2007 году они первыми получили человеческие iPS-клетки.
К числу проблем, с которыми сталкиваются современные методы индуцированной плюрипотентности, относятся очень низкая скорость получения индуцированных плюрипотентных стволовых клеток и тот факт, что 4 транскрипционных фактора, как было показано, обладают онкогенными свойствами.
В июле 2014 года, во время скандала, связанного с японским исследователем стволовых клеток Харуко Обоката, которая фальсифицировала данные, подделывала изображения и плагиатировала работы других, Яманака подвергся публичной критике за свою работу, не имевшую полной документации. Яманака отрицал манипулирование изображениями в своих статьях об эмбриональных стволовых клетках мышей, но он не смог найти лабораторные записи, подтверждающие соответствие исходных данных опубликованным результатам.

С момента первоначального открытия Яманаки в этой области было проведено множество дальнейших исследований, и технология была значительно усовершенствована. Усовершенствования, внесенные в исследования Яманаки, а также перспективы его дальнейших разработок, заключаются в следующем:
  1. Механизм доставки факторов плюрипотентности был усовершенствован. Первоначально использовались ретровирусные векторы, которые случайным образом интегрируются в геном и вызывают дерегуляцию генов, способствующих образованию опухолей. Однако в настоящее время используются неинтегрирующиеся вирусы, стабилизированные РНК или белки, или эписомальные плазмиды (механизм доставки без интеграции).
  2. Были идентифицированы факторы транскрипции, необходимые для индукции плюрипотентности в различных типах клеток (например, в нейронных стволовых клетках).
  3. Были идентифицированы небольшие замещающие молекулы, способные заменить функцию факторов транскрипции.
  4. Были проведены эксперименты по трансдифференцировке . Исследователи пытались изменить судьбу клетки, не проходя через плюрипотентное состояние. Им удалось систематически идентифицировать гены, осуществляющие трансдифференцировку, используя комбинации транскрипционных факторов, которые вызывают переключение судьбы клетки. Они обнаружили трансдифференцировку внутри зародышевых слоев и между зародышевыми слоями, например, экзокринных клеток в эндокринные, фибробластов в миобласты, фибробластов в кардиомиоциты, фибробластов в нейроны.
  5. Клеточная заместительная терапия с использованием индуцированных плюрипотентных стволовых клеток (iPS-клеток) является перспективным направлением. Стволовые клетки могут замещать пораженные или утраченные клетки при дегенеративных заболеваниях и менее подвержены отторжению иммунной системой. Однако существует опасность возникновения мутаций или других геномных аномалий, которые делают их непригодными для клеточной терапии. Таким образом, перед нами стоит множество задач, но это очень перспективное и многообещающее направление исследований. Необходимы дальнейшие исследования для обеспечения безопасности пациентов.
  6. В медицине можно использовать индуцированные плюрипотентные стволовые клетки (iPS-клетки) от пациентов с генетическими и другими заболеваниями для изучения патологических процессов. К таким заболеваниям относятся: боковой амиотрофический склероз (БАС), синдром Ретта, спинальная мышечная атрофия (СМА), дефицит α1-антитрипсина, семейная гиперхолестеринемия и гликогеноз типа 1А. Также их применяют при сердечно-сосудистых заболеваниях, таких как синдром Тимоти, синдром LEOPARD, синдром удлиненного интервала QT 1 и 2 типа; болезнь Альцгеймера, спиноцеребеллярная атаксия, болезнь Хантингтона и др.
  7. Индуцированные плюрипотентные стволовые клетки (iPS-клетки) предоставляют платформы для скрининга при разработке и валидации терапевтических соединений. Например, кинетин был обнаружен в iPS-клетках пациентов с семейной дисфункцией вегетативной нервной системы, а бета-блокаторы и блокаторы ионных каналов при синдроме удлиненного интервала QT были идентифицированы с помощью iPS-клеток.
Исследования Яманаки «открыли новую дверь, и ученые всего мира отправились в долгое путешествие, надеясь найти истинный потенциал наших клеток». 
В 2013 году в Японии с помощью iPS-клеток была создана сосудистая и функциональная печень человека у мышей. Для дифференциации компонентов печени, которые затем самоорганизовались в сложную структуру, использовались множественные стволовые клетки. При помещении в организм мыши сосуды печени соединялись с сосудами хозяина и выполняли нормальные функции печени, включая расщепление лекарств и печеночных секретов. 
В 2022 году было показано, что факторы Яманаки влияют на возрастные показатели у старых мышей. 
Dokar Vita Cells
Международная компания.
Основана в 2019 году.
Dokar Vita Cells — международная компания, основными направлениями деятельности которой являются:

1.Организация лечения клеточными продуктами (Al-BM-MMSC, Экзосомы, NK-клетки, онколитические вирусы) пациентов из разных стран в партнерских клиниках России, Европы, ЮВА.

2. Организация доставки клеточных продуктов (Al-BM-MMSC, Экзосомы, NK-клетки, онколитические вирусы и т.д.) из лабораторий партнеров врачам, клиникам и пациентам.

3.Организация обучения врачей клеточным технологиям.

Компания имеет собственный медицинский совет, в который входят учёные по биологии и медицине, а также опытные врачи.
Этапы производства МСК
Основные этапы производства мезенхимальных стволовых клеток включают различные методы, которые мы рассмотрим ниже.
Подбор здорового донора в возрасте от 18 до 22 лет (это возраст, при котором МСК костного мозга наиболее активные).
Расовая принадлежность донора не имеет значения, поскольку генетический материал (ДНК) донора реципиенту не передается (в связи с тем, что донорские ММСК оказывают лишь паракринное действие, сохраняются в организме пациента около 30 дней, затем происходит апоптоз (гибель ММСК) и они утилизируются лейкоцитами пациента).
DOKAR самостоятельно выбирает доноров. Доноры не должны курить, употреблять алкоголь или употреблять наркотики. У них не должно быть татуировок (татуировка существенно снижает активность ММСК).
Мы проводим исследование состояния здоровья донора, тестирование отсутствия инфекций. Доноры могут сдавать костный мозг 2-3 раза в год. Как правило, наши доноры - студенты и спортсмены. Если МСК доноры показывают высокую активности (оценка по росту, подвижности и экзосомам), то такие доноры стоновятся постоянными (до возраста 25 лет).
Подготовка к забору костного мозга
За 2 дня до забора костного мозга мы проводим обследование донора (общий анализ крови, полный биохимический анализ крови, исследование гормонов, онкомаркеров и инфекций, осмотр ьерапевта). Если все анализы в порядке, мы проводим забор костного мозга. Донор не должен использовать алкоголь, испытывать сильный стресс, заниматься сексом, тренироваться, иметь авиаперелёты за 3 дня до забора костного мозга.
Забор костного мозга у выбранного донора
Костный мозг берут из подвздошной кости в количестве не более 100 мл (этого количества достаточно для производства 14 миллиардов МСК (примерно для 70 внутривенных инъекций по 200 миллионов МСК или 280 локальных инъекций 50 миллионов МСК).
Процедура проводится под местной анестезией (ультракаин) и безболезненна. Донор чувствует себя хорошо.
Костный мозг проверяется (на наличие инфекций, дефектов клеток и активности) и, если все в порядке, начинается процесс культивирования (выращивания МСК).
Культивирование
Выделенную первичную фракцию МСК (МСК с микроокружением (другие клетки, внеклеточный матрикс)) помещают в специальную питательную среду и выращивают в определенных условиях в течение 2-4 дней.
Чистые МСК выделяют из выращенной фракции и проверяют на безопасность и активность. Затем чистую фракцию МСК помещают в другую специальную питательную среду (авторская разработка) и выращивают при определенных условиях (температура, давление, освещение, концентрации О2 и СО2 и т.д.) в течение 4-5 дней.
Полученные ММСК повторно тестируют и готовят к терапевтическому использованию или хранению в криокамере (глубокой заморозке).
Подготовка к терапевтическому использованию
Необходимое количество МСК (чаще всего для внутривенного применения используется 200 миллионов, а для локального - 50 миллионов МСК) помещаются в специальную транспортную среду (авторская разработка) и фасуются во флаконы 10 или 5 мл. Полученные флаконы можно хранить при температуре от 4 до 8 градусов Цельсия в течение 72 часов. Доставка флаконов с МСК осуществляется в специальных контейнерах курьером.
Длительное хранение МСК
Для длительного хранения МСК мы используем криокамеру (-80 градусов Цельсия). Мы разработали собственный протокол заморозки и разморозки МСК с сохранением их активности. В случае подготовки МСК из криокамеры требуется 4-5 дней (мы создали собственный протокол подготовки МСК из криокамеры).
КОНТАКТЫ
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