STEM CELL THERAPY IN UKRAINE AND RUSSIA
Recently, there have been changes in stem cells treatment laws in Ukraine and Russia. Today in Ukraine, more than four clinics and in Russia more than 20 clinics involved in stem cell treatment. In general about 2,000 professionals working in this area.
Specialists working with embryonic stem cells (in vivo), developing indications and contraindications for treatment of severe acquired and genetic diseases that occur with the loss of cell mass. In addition, the clinics conducted a number of treatment conditions such as aging, menopause, infertility, functional disorders of internal organs, chronic fatigue syndrome. All treatments with embryonic stem cells used in the clinics are the property and are protected by patents of Ukraine, Russia, USA and other countries.
In our work we investigated quality of stem cells therapy in Ukraine and Russia.
Treatment in hospitals in Russia and Ukraine – is a complex therapy, including transplantation of embryonic stem cells in conjunction with the general classical treatment. Transplantation of embryonic stem cells – an introduction to the patient progenitor cells that form pools of cells responsible for specific systems and functions of the body: nervous, immune and muscular systems, hematopoiesis, blood circulation, etc., Transplantation of embryonic stem cells requires the least possible interference with the patient ( minimally invasive procedures) – the introduction of cells are intravenously or subcutaneously.
In the treatment in the clinics of Ukraine used the stem cells of different species from different zones of the sprout of the embryo (5-8 weeks), since they are characterized by specific therapeutic effects. Significant results in treatment are achieved by combining different types of stem cells in view of the pathogenesis of the disease.
Sterility and safety of embryonic cell suspensions are guaranteed the use of international standards for testing and compliance with safety regulations when working with biological material.
Clinics in Ukraine and Russia conducts therapy with embryonic stem cells from ethical and scientific standards.
Today, more than 80 % of clinics GCP,GMP certificated.
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Stem cells provide an incredible number of opportunities to improve our understanding of the functioning of the human body. One of the options under consideration is the use of autologous stem cell therapy . Certain interest attracted by the possibility of using stem cells for the treatment of neurodegenerative diseases. In the coming years the volume of clinical application of stem cells for the treatment of Alzheimer’s disease , Parkinson’s disease , amyotrophic lateral sclerosis and multiple sclerosis will increase and , despite the need to comply with great care in promoting potential therapeutic approaches , before use of stem cells hold great promise .
Since its opening, the stem cells changed the perception of experts on the human body and revolutionized the field of medical research . Since then, a greater understanding of the processes of development and repair damage to the human body . Because of this we were able to expand the prospects of using stem cells in the human body . The result has been an increased interest shown in the therapeutic use of stem cells .
Interest in research related to the use of stem cells for the treatment of neurodegenerative diseases such as Alzheimer’s disease , Parkinson’s disease , amyotrophic lateral sclerosis and multiple sclerosis , in the medical environment is constantly growing. Each of these diseases affect different regions and structures of the central nervous system. The use of stem cells in the form of a protective or substitution therapy for the treatment of each of these diseases has a great potential .
Stem cells , the possibilities and limitations of their use
Stem cells have been discovered in the early 60s of the last century [2,3 ] , and the study of their characteristics and composition took a very long time. In general, stem cells are defined as cells capable of self-renewal and differentiation into different cell types. On the basis of the ability to differentiate stem cells can be classified as totipotent , pluripotent or multipotent . Totipotent cells can differentiate into any cell type of an organism, including in extraembryonic tissue. They can be isolated only from embryos situated at the 4- cell stage .
Isolated from the blastocyst pluripotent cells can differentiate into any cell of the body, that is capable of giving rise to cells of any of the three primary germ layers : ectoderm , mesoderm and endoderm . Multipotent cells can be transformed only in certain cell types . They can be isolated from various tissues of adult organism . With the development of his body ‘s ability to differentiate stem cells gradually decreases from totipotency to pluripotency and , ultimately , to multipotency .
By naturally occurring stem cells are mainly embryonic stem cells ( ESCs) , fetal ( fetal ) stem cells and adult stem cells . Blastocysts derived from embryonic stem cells are pluripotent and reproduce quite well in culture. Thus, they correspond to two important requirements: the possibility of obtaining a large number of cells and the ability to give rise to various types of cells [ 4]. From this perspective , the embryonic stem cells are more attractive for clinical use , but their use raises a number of ethical issues [5,6 ] and is associated with the risk of undesirable side effects such as immune response , tumor formation or a combination of both together [ 7].
Multipotent cells can be isolated from fetal organs . These benefits include the ability to adapt to the environment , the ability to migrate , no risk of teratoma formation and rejection under the body .
Traditionally, the adult stem cell is defined as the multipotent cells whose ability to differentiate defined tissue in which they are contained . The endogenous populations of adult stem cells are part of a large number of body tissues, including bone marrow , muscle , brain and liver [1 ] . The main advantage of these cells is the ability to use them for autologous therapy in which the cells are isolated from the patient and subsequently used for his own treatment. This eliminates any ethical issues and risks associated with the use of embryonic stem cells . However , despite their apparent appeal, limited ability to differentiate does not allow adult stem cells to become a versatile therapeutic agent.
Because of the limitations associated with the use of natural variants of stem cells, researchers have developed a method of increasing pluripotency neplyuripotentnyh cells. Cells resulting from such reprogramming via specific transcription factors Oct4, Sox2, Klf4 and c-Myc [9-12], are called induced pluripotent stem cells ( iPSCs ) . Some experts argue that iPS enough for only two of these factors [ 13,14]. Induced CPM allow the use of therapeutic own reprogrammed somatic cells of the patient. However, the possibility of using iPS cells are also limited .
First, the process of creating such cells is ineffective . Therefore, at the initial stage, a large amount of stem cells may cause certain difficulties.
Secondly, the use of viral vectors to transduce pluripotent factors is a problem of their possible integration into the genome of the cells [ 16].
Finally, the iPSCs may give rise to teratomas , although this risk is lower compared to the risk associated with the use of embryonic stem cells [ 16].
Researchers have made several attempts to overcome these difficulties.
The reason for the low efficiency of iPSC reprogramming may be associated with p53 – mediated DNA damage  , therefore, inhibition of p53 activity can increase the yield of iPS cells , but it is associated with an increased risk of tumor formation .
Tried to solve the second problem in two ways . One of them is the use of non- viral transfection [ 18], but in this case remains a problem of low efficiency and long-term control of gene expression can be problematic . The second approach involves the use of viruses that are removed by the enzyme Cre- recombinase  , or the introduction of the recombinant protein . However, scientists still have yet to prove the functionality and safety of the resulting cells, and the development of therapies based on the use of stem cells , there may be other complications , but the future of this area is very promising .
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Treatment of neurodegenerative diseases and stem cell
Treatment of neurodegenerative diseases is one of the potential areas of clinical application of stem cells. Discovery of neural stem cells and the results of subsequent studies [ 21] refuted previously prevailing in the neurobiology of the idea that the central nervous system of adults incapable of neurogenesis [ 22,23]. It turned out that neurogenesis occurs throughout the life of the organism . It is believed that the neural stem cells contained in the sidewall area of supraventricular ventricles and the subgranular zone of the dentate gyrus of the hippocampus , where neurogenesis takes place [ 22,24 ] .
Neural stem cells give rise to glial progenitor cells and neuronal precursor cells . First the ability to differentiate into astrocytes and oligodendrocytes , while the second – in neurons [ 23]. Another study showed that aged rats transplanted neural stem cells isolated from 9 -week fetal human ability to differentiate , and improve the cognitive function of animals [ 25]. Therefore, the idea of using neural stem cells for the treatment of neurodegenerative diseases is very promising.
However, neural stem cells are obtained which are suitable for subsequent therapeutic use is quite difficult. The results of a large number of earlier studies indicate the possibility of using a relatively easily extracted from the bone marrow mesenchymal stem cells ( MSCs ) for obtaining nerve cells. Today, however, scientists agreed that the mesenchymal stem cells are not able to differentiate into nerve cells full . The results of the earlier work the authors suggest that the mesenchymal stem cells can be dedifferentiated to cells , such iPS cells , by increasing gene expression nanog, whose expression is characteristic of embryonic stem cells. After dedifferentiation of such mesenchymal stem cells are unable to transdifferentiate into nerve cells . This indicates that the use of adult stem cells as a source of autologous cells for creating iPS cells . This technology and technique for producing iPS cells open the possibility of developing methods of autologous therapy of neurodegenerative diseases , as well as provide ease of isolation of the patient ‘s own cells . Another key factor in the development of therapies for neurodegenerative diseases with stem cells is the understanding of the mechanisms of the pathogenesis of these diseases. Each disease should be studied separately , and each therapeutic approach should be developed accordingly.
Alzheimer’s disease , and stem cells
Alzheimer’s disease is one of the leading causes of dementia . This disease , which are fundamental markers forming plaques in the brain of beta-amyloid peptide and neurofibrillary bands [ 21,27-29 ] , resulting in the death of several types of neural series in many regions of the brain [ 29-31 ] , especially cholinergic neurons [ 23]. 1987 Public gene amyloid precursor protein is on chromosome 21 and encodes the type I transmembrane protein [ 32].
Plaques of beta- amyloid are formed as a result of cutting the amyloid precursor protein , is effected by enzymes of gamma and beta secretases between certain amino acids [ 33]. Neurofibrillary strands composed of hyperphosphorylated Tau protein [ 34]. Formation of these structures leads to a neuronal damage and, consequently, deterioration of cognitive function and memory loss [ 29]. However, researchers have not yet been able to decipher the direct mechanisms of pathogenesis of Alzheimer’s disease .
Currently available drugs for the treatment of Alzheimer disease , such as cholinesterase inhibitors [ 33,37 ] , allow only to stop the symptoms of the disease [ 36]. After the release of the neurotransmitter acetylcholine from the synapse cholinesterase inhibitors slow down its degradation, which has a beneficial effect on cognitive function . However, preparations of this type have only a moderate effect , the severity of which may vary for different patients [ 38].
The active ingredient of another type of drugs available for the treatment of Alzheimer’s disease is an antagonist of N- methyl -d- aspartate – memantine [ 33]. This prevents excessive stimulation of N-methyl -d- aspartate , which can have toxic effects [ 33]. Given that current treatments have weak effects , the severity of which varies in different patients within a wide range , there is an urgent need for new therapeutic approaches . According to statistical projections, by 2029 the U.S. will be diagnosed annually 615,000 , and by 2050 – 959,000 new cases of Alzheimer’s disease . Such an increase in the incidence will increase the burden on the health system .
Recently Blurton-Jones et al.  published a study in which they injected neural stem cells in the hippocampus, a transgenic mouse model of Alzheimer’s disease and normal animals of the same age . An interesting fact is that the procedure improved the cognitive function of mice had no effect on the existing beta amyloid plaques and neurofibrillary strands . Instead, researchers have identified in the brains of animals increase in brain -derived neurotrophic factor , which plays an important role in the formation of new neurons and synapses , which helped to improve cognitive function by increasing the density of synapses . This demonstrates the possibility of improving the cognitive function without interfering with the existing pathological manifestations .
Despite the fact that the physiological function of the amyloid precursor protein is unclear, recently published data indicate that it may play an important role in regulating the biological functions of stem cells or adult neurogenesis [ 40]. The authors found that amyloid precursor protein increases the levels of chemokines that affect cell migration [ 41]. It was also shown that increased levels of amyloid precursor protein triggers differentiation of human neural stem cells into glial cells as in vitro, and in vivo. This may complicate the process of neurons regeneration by stimulating the division of neural stem cells against a high concentration of amyloid precursor protein . Moreover , high levels of amyloid precursor protein were found in patients with Down syndrome who have a lifetime developing Alzheimer disease, may deplete the endogenous population of neural stem cells due to their increased premature differentiation into glial cells . This feature of amyloid precursor protein , seems to be considered when designing therapies for neurodegenerative diseases at elevated concentrations of the protein in the brain of patients. Elevated levels of amyloid precursor protein in the brain not only reduce the size of the population of neural stem cells , which can increase the risk of developing Alzheimer’s disease, but also stimulate glial differentiation of transplanted stem cells , reducing the effectiveness of therapies aimed at improving cognitive function [ 42,43 ] . Thus, in certain cases, prior to stem cell transplantation is advisable to reduce the level of amyloid precursor protein in brain. This confirms the results of experiments on the transplantation of neural stem cells of transgenic mice with overexpression of this protein in the brain, the concentration of which was reduced using fenserina [ 34]. Neural stem cells can also have a positive effect by increasing the concentration of growth factors. In the transgenic models of Alzheimer’s disease showed improvement in cognitive function due to the release of brain -derived neurotrophic factor after transplantation of neural stem cells [ 29]. The ability of these cells to express a brain -derived neurotrophic factor and stimulate neurite outgrowth as demonstrated by the spinal cord injury model [ 44].
Many experimental studies demonstrate a positive neuroprotective effect hematopoietic growth factors such as granulocyte colony stimulating factor , erythropoietin , granulocyte -macrophage colony stimulating factor, stem cell factor , vascular endothelial growth factor , and the factor 1 -alpha derived stromal cells in ischemic stroke [ 45,46 ] . In an animal model of transient ischemia demonstrated the ability of isolated from bone marrow mesenchymal stem cells protect the brain from ischemic injury or reduce their effects by releasing insulin-like growth factor -1 . Despite the promising results obtained from studies in animal models , the lack of clinical data makes it difficult to assess the effectiveness of the use of growth factors as a therapy for neurodegenerative diseases. In a clinical study of stroke patients administration of mesenchymal stem cells expressed ensured stable improvement Barthel index and the modified Rankin scale compared with patients in the control group during the observation period of 12 months . Conducted after long-term follow-up study results intravenous administration of autologous mesenchymal stem cells in patients with ischemic stroke showed very encouraging results . The results obtained in the future may help in developing methods of using stem cells to improve the levels of growth factors in Alzheimer’s disease .
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3-D Models,Adhesion,Adult stem cells,Aging,ALS/Lou Gehrig’s disease,Alzheimer’s disease,Amniotic Stem Cells,Androgenesis,Anoikis,Antibodies,Apoptosis,Beta Cells,Bio-engineering,Bioinformatics,Bladder,Blastomere,Blood,Blood Vessels,Bone,Bone marrow,Bone Remodeling,Brain,Breast,Bronchioalveolar Stem Cells,C. elegans,Cancer stem cells,Cardiac Lineage,Cardiology,Cartilage,Cell Cycle Regulation,Cell therapy,Cell tracing,Chemical genetics,Chemically defined media,Chick,Chimera,Chromatin,Cilia,Clinical trials,Cow,Culture techniques,Cytokine,Degenerative disorders,ISSCR,Dendritic,Derivation,Development,Diabetes,Directed differentiation,Dopamine Neurons,Drosophila,Drug discovery,Ear,Ectoderm,Embryonal carcinoma cells,Embryonic germ cells,Embryonic stem cells,Endoderm,Epiblast stem cells,Epidermis,Epigenetics,Epithelial,Ethics,Evolution,Extracellular matrix,Eye,FACS,Fat/adipose,Fate Choice,Feeder cells,Fetal stem cells,Gall Bladder,Gene expression,Gene knock-down,Gene regulation,Gene targeting,Gene Therapy,Gene transduction,Genetics,Genomics,Germ cells,GVH/HVG diseases,Hair,Heart,Hematopoiesis,Hematopoietic stem cells,Hepatocyte,High Content Analysis,High throughput screening,Homing,Horse,Human,Human embryonic stem cells,Huntington’s disease,Hypoxia,Imaging,Immortal Strand,Immortalization,Immunology,Imprinting,in vitro,in vivo,Induced Pluripotency,Inducible gene expression,Infertility,Inner Cell Mass,Intestine,IVF/ART,Karyotype,Kidney,Leukemia,Lineage Commitment,Liver,Lung,Lymph,Mammal,Marker,Mass Spectrometry,Mesenchymal stem cells,Mesoderm,Metabolism,Metastasis,MHC/HLA,Microenvironment,MicroRNA,Microscopy,Migration,Mitochondria,Morphogen,Mouse,Multipotent stem cells,Murine,Muscular dystrophy,Neural Crest,Neural stem cells,Neurobiology,New technology,Niche,Nuclear Reprogramming,Nuclear Transfer,Oncology,Oocyte,Organogenesis,Osteogenesis,Ovary,Pancreas,Parkinson’s disease,Parthenogenesis,Patterning,Pig,Placenta,Plant biology,Plants,Pluripotent stem cells,Policy,Polycomb Transcription Factors,Primate,Progenitor cells,Prostate,Prostate Cancer,Proteomics,Rabbit,Rat,Regeneration,Regulatory Standards,Reporter,Reprogramming,Retina,Scaffolds,Senescence,Sheep,Signaling,Silencing,Skeletal Muscle,Skin,Skin stem cells,Smooth Muscle,Spermatogonial stem cells,Spinal cord injury,Spleen,Stability,Stem Cell Tourism,Stomach,Stroke,Synthetic Biology,Teeth,Teratocarcinoma,Teratoma,Testis,Thymus,Tissue engineering,Transcription factors,Transgenics,Transplantation,Umbilical,Vascular Biology,Visualization,Xeno-free culture,Xenopus,Zebrafish,Zygote,,
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