What are stem cells?
Much has been written about stem cells, both informative and deeply scientific articles. However, it is necessary to touch this question again and remind the reader about the main types of stem cells. For simplicity, some of the material is taken from open source Wikipedia.
Stem cell classification
Stem cells can be divided into three main groups depending on the source of their production: embryonic, fetal and postnatal (stem cells of an adult organism).
EMBRYONAL STEM CELLS
EMBRYONAL STEM CELLS Embryonic stem cells (ESCs) form an internal cell mass (ECM), or embryoblast, at an early stage of embryo development. They are pluripotent. An important advantage of ESCs is that they do not express HLA (human leucocyte antigens), that is, they do not produce tissue compatibility antigens. Each person has a unique set of these antigens, and their discrepancy in the donor and recipient is the most important cause of incompatibility in transplantation. Accordingly, the chance that the donor embryonic cells will be rejected by the body of the recipient is very low. It should be noted that clinical trials with the use of differentiated derivatives (derived cells) of ESCs have already begun. To obtain ESCs in the laboratory, it is necessary to destroy the blastocyst in order to isolate the ECM, that is, to destroy the embryo. Therefore, researchers prefer to work not with embryos directly, but with ready-made, previously isolated ESC lines.
Clinical studies using ESCs are subject to particular ethical review. In many countries, ESC studies are limited by law.
One of the main drawbacks of ESCs is the impossibility of using autogenous, that is, its own material, during transplantation, since the extraction of ESCs from the embryo is incompatible with its further development.
FETAL STEM CELLS
Fetal stem cells are obtained from fetal material after an abortion (usually the period of gestation, that is, fetal development, is 9-12 weeks). Naturally, the study and use of such a biomaterial also raises ethical problems. In some countries, for example, in Ukraine and in the UK, work is continuing on their study and clinical application. For example, the British company ReNeuron is exploring the use of fetal stem cells for the treatment of stroke.
POSTNATAL STEM CELLS
Despite the fact that the stem cells of the mature organism are less potent than the embryonic and fetal stem cells, that is, they can produce fewer different types of cells, the ethical aspect of their research and use does not cause serious controversy.
In addition, the possibility of using autogenic material ensures the effectiveness and safety of treatment. The stem cells of an adult organism can be divided into three main groups: hematopoietic (hematopoietic), multipotent mesenchymal (stromal), and tissue-specific progenitor cells. Sometimes, umbilical cord blood cells are separated into a separate group, since they are the least differentiated of all cells of a mature organism, that is, they have the greatest potency.
Umbilical cord blood mainly contains hematopoietic stem cells, as well as multipotent mesenchymal cells, but it also contains other unique stem cell types that under certain conditions can differentiate into cells of various organs and tissues.
Hemopoietic Stem Cells
Hematopoietic stem cells (HSC) are multipotent stem cells that give rise to all myeloid blood cells (monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes, and red blood cells, and lymphoid cells, and red blood cells, megakaryocytes, and red blood cells, and lymphoid row and red blood cells, megakaryocytes, and lymphoid row and erythrocytes, erythrocytes, megakaryocytes) killers).
The definition of hematopoietic cells has been thoroughly revised over the past 20 years. Hematopoietic tissue contains cells with long-term and short-term capabilities for regeneration, including multipotent, oligopotent, and progenitor cells. Myeloid tissue contains one HSC per 10,000 cells. HSCs are heterogeneous populations.
There are three subpopulations of HSC, in accordance with the proportional ratio of lymphoid offspring to myeloid (L / M). In myeloid-oriented HSCs, low L / M ratio (> 0, <3), in lymphoid-oriented ones, high (> 10). The third group consists of “balanced” HSCs, for which 3 ≤ L / M ≤ 10. Currently, the properties of different groups of HSCs are being actively studied, but intermediate results show that only myeloid-oriented and “balanced” HSCs are capable of prolonged self-reproduction.
In addition, transplantation experiments have shown that each group of HSCs mainly recreates its own type of blood cells, which suggests the presence of an inherited epigenetic program for each subpopulation.
Prior to the use of cord blood, the bone marrow was considered the main source of HSCs. This source and today is widely used in transplantation. HSCs are located in the bone marrow in adults, including the femur, rib, sternum mobilization and other bones. Cells can be obtained directly from the thigh with a needle and syringe, or from the blood after pre-treatment with cytokines, including G-CSF (granulocyte colony-stimulating factor), which promotes the release of bone marrow cells.
The second most important and promising source of GSK is cord blood. Concentration of HSC in cord blood is ten times higher than in the bone marrow. In addition, this source has several advantages. The most important of them are:
Age. Cord blood is collected at the earliest stage of the organism’s life. Cord blood glucose cells are maximally active because they have not been adversely affected by the external environment (infectious diseases, unhealthy food, etc.). Cord HSCs are able to create a large cell population in a short time.
Compatibility. The use of autologous material, that is, own cord blood, guarantees 100% compatibility. Compatibility with brothers and sisters is up to 25%, as a rule, it is also possible to use the cord blood of a child for the treatment of other close relatives. For comparison, the probability of finding a suitable stem cell donor is from 1: 1000 to 1: 1000 000.
MULTIPOTENT MESENCHYMAL STROMAL CELLS
Multipotent mesenchymal stromal cells (MMSC) are multipotent stem cells capable of differentiating into osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells), cardiomyocytes, nervous tissue, hepatocytes. The properties of MMSC are constantly being studied and every year new abilities are opened up to transform these cells into other types of cells and tissues.
The precursors of MMSC in the embryogenic period of development are mesenchymal stem cells (MSCs). They can be found in the areas of distribution of the mesenchyme, that is, the germinal connective tissue.
The main source of MMSC is the bone marrow. In addition, they are found in adipose tissue and a number of other tissues with good blood supply. There is some evidence that the natural niche of the MMSC is located perivascular – around blood vessels. In addition, MMSCs were found in the pulp of milk teeth, amniotic (amniotic fluid), cord blood and Warton gum. These sources are investigated, but rarely used in practice.
For example, the release of young MMSCs from Varton jellus is an extremely time-consuming process, since the cells in it are also located perivascularly. In 2005–2006, specialists in MMSK officially determined a number of parameters to which the cells must correspond in order to classify them in the MMSK population. There have been published articles that present the immunophenotype of MMSC and the directions of orthodox differentiation. These include differentiation into cells of bone, adipose and cartilage tissues.
A number of experiments were carried out to differentiate MMSCs into neuron-like cells, but researchers still doubt that the neurons obtained are functional. Experiments are also carried out in the field of MMSC differentiation into myocytes – muscle cells. The most important and most promising area of clinical application of MMSC is co-transplantation together with HSC in order to improve engraftment of a bone marrow sample or cord blood stem cells.
Numerous studies have shown that human MMSCs can avoid rejection during transplantation, interact with dendritic cells and T lymphocytes, and create an immunosuppressive microenvironment through the production of cytokines.
It has been proven that the immunomodulatory functions of human MMSC are enhanced when they are transplanted into an inflamed environment with elevated levels of gamma-interferon. Other studies contradict these conclusions, which is due to the heterogeneous nature of isolated MSCs and significant differences between them, depending on the method of cultivation.
Tissue-specific progenitor cells
Tissue-specific progenitor cells (progenitor cells) are low-differentiated cells, which are located in various tissues and organs and are responsible for updating their cell population, that is, replacing dead cells. These include, for example, mysatellitocytes (precursors of muscle fibers), lympho- and myelopoiesis precursor cells. These cells are oligo-and unipotent and their main difference from other stem cells is that the progenitor cells can only be divided a certain number of times, while other stem cells are capable of unlimited self-renewal. Therefore, their affiliation with true stem cells is questioned. Neural stem cells, which also belong to the group of tissue-specific, are studied separately. They differentiate during the development of the embryo and during the fetal period, as a result of which all the nervous structures of the future adult organism are formed, including the central and peripheral nervous systems. These cells were also found in the CNS of an adult organism, in particular, in the subependymal zone, in the hippocampus, olfactory brain, etc. Despite the fact that most of the dead neurons are not replaced, the process of neurogenesis in the adult CNS is still possible due to neural stem cells, that is, the population of neurons can “recover”, but it occurs in such a volume that does not significantly affect the outcome of pathological processes.
In addition to the above types of stem cells from traditional sources, a new source has recently emerged – Induced Pluripotent Stem Cells (induced pluripotent stem cells, iPSC or iPS).
This completely new type was obtained from the cells of various tissues (primarily fibroblasts) by reprogramming them using genetic engineering methods.
In the early works, iPS tried to get by merging “adult” cells with ESCs. In 2006, iPS was obtained from spermatogonia of mice and humans.
In 2008, methods were developed for reprogramming “adult” cells by introducing “embryonic” genes into them (primarily the genes of the transcription factors Oct4, Sox2, Klf4, c-Myc and Nanog) using adenoviruses and other vectors ”. reprogramming can be induced by transient expression of the introduced genes, without their insertion into the genome of cells. Reprogramming cells to transform them into iPS was recognized by Science magazine as the main scientific breakthrough in 2008.
In 2009, a paper was published in which using the tetraploid complementation method for the first time it was shown that iPS can produce a full-fledged organism, including its germ-line cells. iPS, obtained from the fibroblasts of the skin of mice using transformation using a retroviral vector, in a certain percentage of cases gave healthy adult mice that were able to reproduce normally. Thus, for the first time, cloned animals were obtained without admixture of the genetic material of the eggs (in the standard cloning procedure, the mitochondrial DNA is transmitted to the progeny from the recipient’s egg).
Shinya Yamanaka is a Japanese scientist, professor at the Institute of Advanced Medical Sciences (Institute for Frontier Medical Sciences) at Kyoto University, director of the Center for iPS Cell Research and Application (Kyi University), a leading researcher at the Institute of Cardiac – Vascular Diseases Gladstone, San Francisco.
Winner of the Nobel Prize in Physiology and Medicine 2012.
In 2006, for the first time in the world, he received induced pluripotent stem cells (iPS cells), thanks to which he gained worldwide fame, and in 2012 he received the Nobel Prize in Physiology or Medicine for this work with the English scientist John Gurdon.
Concluding a brief overview of stem cell types, it should be noted that in clinical practice, not all cell types and not any diseases are used to treat diseases.
Autologous (own) patient’s cells obtained from adipose tissue, bone marrow or cord blood are considered the most “safe” for use in medical practice, other cell types undergo various stages of clinical trials and will soon take their place in the arsenal of therapeutic tools of cellular therapy.