The global prevalence of diabetes mellitus and its severe complications is on the rise. The study of the pathogenesis of the onset and the progression of complications related to the disease, as well as the search for new therapeutic agents and methods of treatment, remains relevant. Experimental models are extremely important in the study of diabetes. This survey contains a synthesis of the most commonly used experimental animal models described in scientific literature. The mechanisms of the streptozotocin model are also analyzed and discussed, as it is considered as the most adequate and easily reproducible diabetes model. A review of the significant advantages and disadvantages of the described models has also been conducted.
Mouse submandibular salivary gland cells and liver progenitor cells from long-term in vitro cultures with a high proliferation potential were side-by-side compared by methods of immunocytochemistry, quantitative real-time PCR, flow cytometry, and transcriptome analysis. The two cell types were found to be similar in expressing cell markers such as EpCAM, CD29, c-Kit, Sca-1, and c-Met. In addition, both cell types expressed cytokeratins 8, 18, and 19, alpha-fetoprotein, and (weakly) albumin. Unlike the liver cells, however, the salivary gland cells in culture showed high-level expression of cytokeratin 14 and CD49f, which was indicative of their origin from salivary gland ducts. Quantitative real-time PCR and deep-sequencing transcriptome analysis revealed similarities in the expression pattern of transcription factors between the two cell types. In this respect, however, the cultured salivary gland cells proved to be closer to exocrine cells of the pancreas than to the liver progenitor cells. Thus, ductal cells of postnatal submandibular salivary glands in culture show phenotypic convergence with progenitor cells of endodermal origin, suggesting that these glands may serve as a potential cell source for cellular therapy of hepatic and pancreatic disorders. The results of this study provide a deeper insight into the molecular features of salivary gland cells and may help optimize procedures for stimulating their differentiation in a specified direction.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-183) contains supplementary material, which is available to authorized users.
Circahoralian, or ultradian, intracellular rhythms, including protein synthesis rhythm, were described in various cells both in situ and in vitro (for reviews see Brodsky, 1975; Ultradian Rhythms …, 1992). They have been studied for a long time in the cultures of hepatocytes as well. Visualization of any rhythm in a cell culture is only possible when oscillations are synchronized due to intercellular cooperation. The rhythm expression depends on the degree of synchrony, i.e., on cooperative activity of cell in the formation of an aggregate rhythm of a cell population. The amplitude of rhythm, or range of oscillations, is a visible reflection of this cooperation. In the case when each individual cell has a rhythm, but oscillations in different cells are antiphasic, the aggregate kinetics of a population will not be oscillatory. When the phases of oscillations correspond to each other, a rhythm is visualized and, the closer the phases of oscillations of individual cells, the higher the amplitude of the aggregate rhythm.We have already shown that the amplitude of oscillations of protein synthesis intensity in the cultures of hepatocytes from old rats is lower than that from young animals (Brodsky et al. , 2001), which characterized a low cooperative activity of the cells of old animals. However, these data were preliminary: we assayed the kinetics of protein synthesis only in two old rats. In order to confirm the first observations, it was necessary to carry out experiments of a larger material and, in case of a positive result, clarify possible causes of agerelated changes and establish to what extent they are reversible.When studying intercellular cooperation, we investigated dense, fast self-synchronizing in a fresh medium, hepatocytes and sparse asynchronous cultures (Brodsky et al. , 1994(Brodsky et al. , , 1996a. We used the synchronizers we found earlier: gangliosides (Brodsky et al. , 1996a(Brodsky et al. , , 1997Zvezdina et al. , 2000). Gangliosides are cell membrane glycolipids; they are constantly secreted in extracellular medium and incorporated in other cells and affect many intracellular processes (for reviews see Hakomori, 1981Hakomori, , 2000Tettamanti and Riboni, 1994;Yates and Rampersaud, 1998). In our experiments, asynchronous sparse cultures of hepatocytes were synchronized soon after addition of a standard mix of bovine brain gangliosides (BBG: 20% GM1, 40% GD1a, 16% GD1b, and ca. 4% of others) or individual fractions (GM1 or GD1a). The synchronizing effect of gangliosides can be reproduced by a medium conditioned by dense cultures (Brodsky et al. , 1995(Brodsky et al. , , 2000b.In order to simulate the influence of gangliosides on intracellular processes, we studied their well known effect on the concentration of calcium ions in the cytoAbstract -Cell interactions have been studied in cultures pf hepatocytes from young and old rats. The rhythm of protein synthesis is an index of cell interaction and synchronization in culture, while the amplitude of oscillations characterized cell cooperation i...
Diabetes affects over 350 million people worldwide, with the figure projected to rise to nearly 500 million over the next 20 years, according to the World Health Organization. Insulin-dependent diabetes mellitus (type 1 diabetes) is an endocrine disorder caused by an autoimmune reaction that destroys insulin-producing -cells in the pancreas, which leads to insulin deficiency. Administration of exogenous insulin remains at the moment the treatment mainstay. This approach helps to regulate blood glucose levels and significantly increases the life expectancy of patients. However, type 1 diabetes is accompanied by long-term complications associated with the systemic nature of the disease and metabolic abnormalities having a profound impact on health. Of greater impact would be a therapeutic approach which would overcome these limitations by better control of blood glucose levels and prevention of acute and chronic complications. The current efforts in the field of regenerative medicine are aimed at finding such an approach. In this review, we discuss the time-honored technique of donor islets of Langerhans transplantation. We also focus on the use of pluripotent stem and committed cells and cellular reprogramming. The molecular mechanisms of pancreatic differentiation are highlighted. Much attention is devoted to the methods of grafts delivery and to the materials used during its creation.
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