Potential therapeutic application of mesenchymal stem cells in ophthalmology

At present a wide variety of methods have been proposed to treat eye disorders, drug therapies are most commonly used. It should be noted that effective treatment modalities especially for degeneration of the retina and optic nerve are lacking. In the last few years stem cell transplantation has been proposed as an alternative method. The opportunities that stem cells provide within clinical use are almost unlimited. These cells are presently applied to treat various traumatic and degenerative disorders due to their unique biologic properties. Stem cells have high proliferative capabilities and are a self-maintained population of cells capable of differentiating into different cell types. Thus, they are represent a very primary stage of a cell lineage. Their ability to differentiate into different pathways provides animals with great plasticity in the renewal of somatic cells in postnatal ontogenesis. Pre-clinical and clinical ophthalmology studies where mesenchymal stem cells are applied and various methods of their administration are discussed herein. In addition the safety and efficacy of using bone marrow- and adipose tissue-derived mesenchymal stem cells have been discussed

Modern methods of preclinical anticancer drug screening using test systems based on cell cultures

Preclinical screening of medicinal drugs for novel anti-cancer treatments faces a problem of a rational approach to primary screening of substances with antitumor activity. Low correlation between in vitro and in vivo studies with clinical trials remains a serious issue. Choosing the right tumor model at the in vitro testing stage reduces the financial and time costs of finding and testing promising antitumor agents. In the light of the growing prevalence of cancer, it is urgently important to develop new approaches to screening of anticancer drugs, as well as to increase the pace of creation, development, and testing of new antitumor agents. Although the pharmaceutical industry uses mainly two-dimensional in vitro models, the field of preclinical screening needs more complex models, such as three-dimensional models, microfluidic systems, Boyden chamber, and models created using three-dimensional bioprinting. This review describes the above in vitro tumor models, including their use in research and features, in order to help researchers and clinicians from various fields of pharmacy, preclinical studies, and cell biology understand their prospects for screening potential antitumor drugs

Mitochondria Donation by Mesenchymal Stem Cells: Current Understanding and Mitochondria Transplantation Strategies

The phenomenon of mitochondria donation is found in various tissues of humans and animals and is attracting increasing attention. To date, numerous studies have described the transfer of mitochondria from stem cells to injured cells, leading to increased ATP production, restoration of mitochondria function, and rescue of recipient cells from apoptosis. Mitochondria transplantation is considered as a novel therapeutic approach for the treatment of mitochondrial diseases and mitochondrial function deficiency. Mitochondrial dysfunction affects cells with high energy needs such as neural, skeletal muscle, heart, and liver cells and plays a crucial role in type 2 diabetes, as well as Parkinson’s, Alzheimer’s diseases, ischemia, stroke, cancer, and age-related disorders. In this review, we summarize recent findings in the field of mitochondria donation and mechanism of mitochondria transfer between cells. We review the existing clinical trials and discuss advantages and disadvantages of mitochondrial transplantation strategies based on the injection of stem cells, isolated functional mitochondria, or EVs containing mitochondria

Tay-Sachs disease: Diagnostic, modeling and treatment approaches

© 2020, Human Stem Cell Institute. All rights reserved. Tay-Sachs disease (OMIM 272800) belongs to the group of autosomal-recessive disorders, caused by β-hexosaminidase A (HexA) enzyme deficiency, resulting in GM2-ganglioside accumu-lation in nervous and other tissues of the body. Enzyme deficiency is caused by various mutations in HEXA gene. Clinical symptom severity depends on residual HexA enzymatic activity associated with some mutations. Currently, there is no effective treatment for Tay-Sachs disease. There are clinical reports of substrate reduction therapy, bone marrow or umbilical cord blood transplanta-tion. However, the therapeutic efficacy of these methods remains insufficient to prevent aggravation of neurological symptoms in Tay-Sachs disease patients. Encouraging results were obtained using gene therapy to deliver wild-type genes encoding the α and β subunits of HexA. This review discusses the therapeutic strategies in Tay-Sachs disease treatment, as well as diagnostic methods and existing animal models to evaluate the effectiveness of new approaches for Tay-Sachs disease therapy

COVID-19: is transmission through eye contact possible?

The article reviews international and Russian scientific papers concerning the possibility of transmitting coronavirus infections, particularly the COVID-19, through eye surface. According to the studied literature, the incidence of ocular symptoms in CO-VID-19 is around 0.8—31.6%, with conjunctivitis being the most frequent manifestation. The review summarizes data on virus detection in conjunctival discharge of COVID-19 patients. Across six studies, the total number of patients is 252, among which were 8 cases (3.17%) of virus detection in the conjunctival cavity. The review discusses the reasons for infrequent detection of the virus in the lacrimal fluid. The analyzed data shows that COVID-19 associated conjunctivitis can be the first symptom, the primary manifestation, or sometimes be detected in the lacrimal fluid of patients without any concomitant signs of eye surface inflamma-tion. The article also presents two clinical cases of patients with keratoconjunctivitis and conjunctivitis associated with COVID-19, as well as the results of experimental transconjunctival and respiratory exposure of Rhesus macaques to SARS-CoV-2 with conclusion of possibility of this type of transmission. Additionally, the review contains the opinion of researchers concerning the influence of several factors on the possibility of virus detection in the lacrimal fluid. The conclusion was made that there is possibility of COVID-19 transmission through the eye surface. While it is not being considered a major transmission route, it should not be ig-nored. Conjunctival cavity of COVID-19 patients can be the source of infection. Eye protection measures should be undertaken when working with potentially infected patients

Cell Culture Based in vitro Test Systems for Anticancer Drug Screening

© Copyright © 2020 Kitaeva, Rutland, Rizvanov and Solovyeva. The development of new high-tech systems for screening anticancer drugs is one of the main problems of preclinical screening. Poor correlation between preclinical in vitro and in vivo data with clinical trials remains a major concern. The choice of the correct tumor model at the stage of in vitro testing provides reduction in both financial and time costs during later stages due to the timely screening of ineffective agents. In view of the growing incidence of oncology, increasing the pace of the creation, development and testing of new antitumor agents, the improvement and expansion of new high-tech systems for preclinical in vitro screening is becoming very important. The pharmaceutical industry presently relies on several widely used in vitro models, including two-dimensional models, three-dimensional models, microfluidic systems, Boyden’s chamber and models created using 3D bioprinting. This review outlines and describes these tumor models including their use in research, in addition to their characteristics. This review therefore gives an insight into in vitro based testing which is of interest to researchers and clinicians from differing fields including pharmacy, preclinical studies and cell biology

Tumor microenvironment: A key contributor to cancer progression, invasion, and drug resistance

The tumor microenvironment is composed of extracellular matrix proteins, mostly collagen, and a wide range of tumor-associated cells, including fibroblasts, neutrophils, macrophages, and blood vessels. These components play a crucial role in supporting tumor growth and proliferation, especially at the early stages of metastasis, as well as determine the physiology of tumor cells. Within the tumor microenvironment, the interaction between tumor cells and tumor-associated cells does not only lead to tumor growth and metastasis, but also induces the epithelial-mesenchymal transition and angiogenesis and contributes to the development of drug and radiation treatment resistance. Ion channels and transporters are the important elements in the drug resistance of tumor cells. Advancing our understanding of the tumor microenvironment and its processes encouraging tumor progression is of paramount importance for creating effective targeted antitumor drugs of high specificity, i.e., drugs suppressing stromal and immune components of the tumor microenvironment, as well as at extracellular matrix, angiogenic factors, ion channels and transporters. In this review, we describe the main processes and interactions taking place in the tumor microenvironment and influencing the efficacy of antitumor therapy. We also take a look at stromal and immune cells involved in the tumor development and factors mediating the drug resistance in patients with cancer

Comparative characteristics of mesenchymal stem cell lines from different animal species

In recent years, in veterinary medicine, there have been increasing reports of cell therapy using animal mesenchymal stem cells (MSCs). In most of these investigations, animal MSCs are described without the necessary immunophenotypic characteristics, and in vitro differentiation is rarely performed. The lack of specific single marker for MSCs and limited availability of animal MSCs antibodies complicate these studies. In this work, we described the immunophenotypes of MSCs lines isolated from the subcutaneous adipose tissue of dogs, cats, horses, pigs, mice, rats, and humans. The data obtained showed a successful differentiation in the osteogenic, chondrogenic and adipogenic lineage for all cells

Adenoviral Vector Delivery of vegf, Angiogenin, and gdnf Genes Promotes Angiogenesis in Ischemic Skeletal Muscle

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Effects of adenoviruses carrying genes of a vascular endothelial growth factor (vegf 165), a glial-cell derived neurotrophic factor (gdnf), and angiogenin (ang) were studied in a rat model of chronic hindlimb ischemia. Therapeutic genes were used for direct gene therapy in the following combinations: (1) Ad5-ANG; (2) Ad5-VEGF+Ad5-ANG; and (3) Ad5-VEGF+Ad5-ANG+Ad5-GDNF. Real-time PCR demonstrated increased gdnf, vegf, and ang mRNA levels within the area of an ischemic muscle on day 14 where the study combinations of therapeutic genes were injected in both Ad5-VEGF+Ad5-ANG and Ad5-VEGF+Ad5-ANG+Ad5-GDNF groups. On post-injection day 28, the number of centronuclear myotubes (CNMs) as well as the CD31-immunopositive cell count showed a 38.7- and 1.3-fold increase, respectively, within the ischemic area in the Ad5-VEGF+Ad5-ANG+Ad5-GDNF group compared with the Ad5-VEGF+Ad5-ANG group. There was an increased expression of desmin mRNA in the area of an ischemic muscle in Ad5-VEGF+Ad5-ANG and Ad5-VEGF+Ad5-ANG+Ad5-GDNF groups on day 14. Based on Western blotting results, the expression of CD34 and a von Willebrand factor (VWF) increased on day 14 after injection of Ad5-VEGF+Ad5-ANG+Ad5-GDNF as compared with the control group. The Ad5-VEGF+Ad5-ANG+Ad5-GDNF injection stimulates muscle regeneration by increasing the number of CNMs and blood vessels. Based on the above findings, the gdnf angiogenic and regenerative potential necessitates further studies of its possible use as an agent stimulating angiogenesis and skeletal muscle regeneration for clinical purposes

Genetic Modification of Mesenchymal Stem Cells for Neurological Disease Therapy: What Effects Does it Have on Phenotype/Cell Behavior, Determining Their Effectiveness?

© 2020, Springer Nature Switzerland AG. Mesenchymal stem cells are a promising tool in regenerative medicine, and their functions can be enhanced through genetic modification. Recent advances in genetic engineering provide several methods that enable gene delivery to mesenchymal stem cells. However, it remains to be decided whether genetic modification of mesenchymal stem cells by vectors carrying reporter or therapeutic genes leads to adverse effects on morphology, phenotypic profiles, and viability of transplanted cells. In this regard, we focus on the description of genetic modification methods of mesenchymal stem cells, their effectiveness, and the impact on phenotype/cell behavior/proliferation and the differentiation ability of these cells in vitro and in vivo. Furthermore, we compare the main effects of genetically modified mesenchymal stem cells with native mesenchymal stem cells when applied in the therapy of neurological diseases