Journal of Cellular Biotechnology - Volume 1, issue 1
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Journal of Cellular Biotechnology is a peer-reviewed international journal for advancing research activities in the field of cellular biotechnology. It serves as a medium for the publication of full papers, invited reviews, short communications, technical notes and letters to the Editor-in-Chief on all aspects of cellular biotechnology. This comprises molecular biological topics covering biochemical, chemical, pharmacological or bioprocess engineering aspects, as well as the development of novel biomaterials. Therefore, cellular biotechnology differs from biology, biochemistry, and other basic life sciences by its emphasis on using the knowledge of bioscience to solve important practical problems. Papers presenting information of a multidisciplinary nature - not suitable for publication in a journal devoted to a single discipline - are particularly welcome.
Manuscripts submitted for the
Journal of Cellular Biotechnology are expected to cover activities related to molecular diagnostics, the expansion of human primary cells for individualized therapies or drug testing, 2- and 3-dimensional co-culture techniques, cell line validation, tissue engineering, and stem cell biology for the treatment of human pathologies. This includes studies on the design of reactors and research on cellular biology and physiology of mammalian cells in vitro and in vivo, and tissue. Of special interest is the rational manipulation of reactions through metabolic engineering techniques or specific reactor operations that lead to biomaterials with unique properties. Also, biochemical and physiological studies of metabolism and enzymes as relevant for tissue culture cells, investigations at the molecular level including transcription/translation control; design and engineering of products by molecular strategies; engineering of cellular modification and transport systems such as post-translational protein modifications as well as protein and metabolite secretion; molecular strategies of screening for new or modified products (e.g. pharmaceuticals or bioactive compounds). In addition, investigations in preclinical animal experiments are welcome.
The endeavour of the Editor-in-Chief and publisher of the
Journal of Cellular Biotechnology is to bring together contributions from those working in various fields related to cell-cell or cell-material interactions all over the world. The editorial board members of the
Journal of Cellular Biotechnology are from those countries in Europe, Asia, Australia and America where appreciable work in cellular biotechnology is being carried out. Each editor takes responsibility to decide on the acceptance of a manuscript. He/she is required to have the manuscript appraised by two referees and may be one of them himself. The executive editorial office, to which the manuscripts have been submitted, is responsible for rapid handling of the reviewing process.
Abstract: BACKGROUND: The “Isolated lung perfusion system” has been established to study lung physiological parameters of mice or other small animals, but little is known about the influence of age on the lung function in mice. METHODS: We used a buffer-perfused lung system with negative-pressure ventilation to study the effect of age on physiological parameters in the isolated mouse lung. Our study included C57BL/6N mice when they were young (3 to 4 months), adult (5 to 9 months) or old (24 months). RESULTS: The ex vivo data indicated that maximal function of…the lung is achieved in the early adulthood (5 to 6 months of age). In this period, lung developed highest maximal expiratory flow rate which declined steadily with increasing age. After this age (>7 months) the dynamic lung compliance increased with significant changes in the 24-month-old mice. However, mouse age had no effect on airway resistance and pulmonary artery pressure. Moreover, we did not find an influence of age on the integrity of the endothelial-epithelial barrier. CONCLUSION: Our findings indicate the importance of age, in particular on the respiratory mechanics in isolated mouse lungs, which should be considered in the pulmonary research using the “Isolated lung perfusion system”.
Abstract: Detoxification of xenobiotics including drugs is catalyzed by liver phase I and phase II enzymes. There are three main families of phase I cytochrome P450 (CYP450) monoxygenases that introduce polar groups on drugs. These phase I metabolites can then be further conjugated by transferases during phase II reaction. Liver biotransformation can also lead to toxic drug metabolites, the most common cause of drug failure during clinical investigation. CYP3A4 is considered to be the most important enzyme in drug metabolism. Drug development relies on the use of human liver cells in order to investigate drug metabolism and potential toxicity. With primary…human liver cells as the gold standard several problems have to be solved, i.e. scarcity of functional human liver tissue, donor variation of CYP activity and rapid dedifferentiation processes during primary cell cultivation. These features make it difficult to use primary human liver cells as standard to measure CYP activity. To avoid problems with primary human liver cells, many attempts have been undertaken to establish liver carcinoma cell lines, non-transformed proliferating human liver cell systems and induced pluripotent stem cell-derived hepatocytes. Due to different problems with these surrogate systems, the one cell line that could be used as convenient standard cell system to benchmark CYP3A4 enzyme activity has not been established yet. Based on the widely used hepatocellular carcinoma cell line HepG2 and a lentiviral vector system, we generated cell clones for stable CYP3A4 overexpression. Here we present data on a new HepG2 cell clone (clone 9) showing higher than 10,000-fold overexpression of CYP3A4 compared to HepG2 parental cells. As measured by conversion of testosterone into 6β-hydroxytestosterone, we found an enzyme activity of about 600 pmol per minute per mg total cellular protein, which ranges at the upper end reported for primary human liver cells. This enzyme activity appeared to be kept stable in clone 9 cells, because there was no influence detectable when cells were treated with 5-azacytidine, a drug that interferes with epigenetic silencing processes. Prototypic CYP3A4 inducer rifampicin led to significant increase of CYP3A4 testosterone hydroxylase activity in HepG2 clone 9 cells. Altogether, HepG2 clone 9 strongly and stably overexpressed CYP3A4 leading to a physiological enzyme activity, which apparently was unaffected by epigenetic processes. Thus, HepG2 clone 9 could be a useful reference cell clone for CYP3A4 enzyme activity.
Abstract: The dental pulp is an important soft connective tissue which is able to produce dentin over time as a reaction on external stimuli. It also maintains the biological and physiological vitality of the dentin. Due to this the pulp is essential for teeth homeostasis. However, dental caries is still one of the most prevalent health problems in dentistry and therefore, one major cause for early loss of the dental pulp vitality and subsequent tooth extractions. Meanwhile the potential for successful pulp regeneration therapy is increasing due to advances in the field of regenerative endodontics. Thus, adequate experimental animal models are…required for testing and validating these new regenerative therapies. Rodents and rats in particular, are relevant models for experimental periodontal research. The breeding and housing costs of rats are relatively low facilitating studies with sufficient numbers for statistical analysis in comparison to bigger sized mammals like beagle dogs, miniature pigs or monkeys. Additionally, rat molar teeth and pulps are characterized by similar anatomical, histological, biological and physiological features to human teeth. Essential biological reactions of the pulp tissue and the interaction during the different stages of wound healing of rat molar teeth are comparable to that of other mammals. However, despite of the multiple research activities in the field of regenerative endodontics and the above mentioned advantages of the rat model only rare in vivo studies are published. Therefore, the presented study aimed to introduce the rat molar teeth as a valid model for studying dental pulp stem cell based endodontic tissue regeneration. Human dental pulp stem cells were implanted into the pulp of immunodeficient rats (RNU rats). Cell growth was supported by a collagenous membrane, which was applied on top of the cells after implantation. After closing the pulpal cavity with a light-polymerisable resin human dental pulp stem cells were able to maintain cell viability in the rat molar pulp niche for at least three weeks. This demonstrated the suitability of immunodeficient RNU rats for non-autologous dental stem cell based endodontic tissue engineering approaches.
Abstract: Changes in the microstruture of blood caused by the red blood cell aggregation phenomenon affect the mechanical properties of the fluid. This fact has been extensively investigated in the past and it has been verified that the formation of rouleaux (the characteristic coin-pile like structures) and aggregates at low shear rates affect the flow and as a consequence the viscosity of the fluid is elevated. At physiological red blood cell concentrations and at low shear rates, however, in addition to rouleaux and aggregate formation an extended network is observed. The effects of network characteristics on the mechanical properties of blood…have received relatively little attention in the literature and only a few studies provide quantitative data on this aspect of the blood flow. Quantitative data on network characteristics in view of the aggregation phenomenon illustrate that indeed different network configurations have different effects on the mechanical properties of the fluid. In this work, it is shown that changes in the viscosity of blood at specific flow conditions correlate with the changes in the mechanical characteristics of the red blood cell network.
Keywords: Red blood cell aggregation, microstructure, network, viscosity
Abstract: The purpose of this study was to estimate drug effect on red blood cell (RBC) microrheological properties making for blood transport efficiency. It is well known that blood flow in microcirculation, tissue perfusion and oxygenation depend on red blood cell (RBC) microrheological properties, namely deformability (RBCD) and aggregability (RBCA). In turn the changed red cell mechanical properties can influence the tissue oxygenation as well as the drug delivery to tissues. The exposure of RBCs to agonist of β-adrenergic receptors (isoproterenol) caused RBCA decrease and an increase of their deformability. The prostaglandin E1, prostacyclin and insulin showed the similar positive…microrheological effect. Neutral microrheological effect was fixed after cell incubation with 5-fluorouracil, rolipram and phorbol 12-myristate 13-acetate; no significant alterations of microrheological properties were found. The agonists of α-adrenergic receptors and prostaglandin F2 α showed the negative microrheological effect: RBCD was markedly worsened and RBCA was enhanced by 49–60%. It was found that three PDE inhibitors: vinpocetine, rolipram and cilostasol – significantly decreased RBCA and increased RBCD. Therefore PDEs might be considered as red blood cell molecular targets for some drugs. Stimulated by A23187 Ca2+ influx was accompanied by an increase of RBCA and a decrease of RBCD. The blocking of Ca2+ entry into the RBCs by verapamil led to a significant positive RBC changes. Therefore the red cell membrane Ca2+ channels can be considered as molecular targets responsible for red cell microrheology modifications too. Taken together the obtained data showed that the drugs infused in blood flow can interact with blood cells, including the most numerous cell population – red blood cells. This interaction can lead to an alteration of RBC microrheological properties and blood transport possibilities at least according to three abovementioned scenarios.
Keywords: Red blood cell aggregation and deformability, drugs, microrheological effect, cellular signaling pathways
Abstract: Metabolic syndrome greatly increases the risk for developing metabolic and cardiovascular disorders and has reached epidemic proportions globally. Despite recent advances in medical science, scientific understandings on the root mechanisms of metabolic syndrome are still not fully understood, and such insufficient knowledge contributes to the relative lack of effective treatments for such diseases. Protein Kinase R (PKR) is a serine threonine kinase activated during various stress conditions. Activation of PKR can increase reactive oxygen product generation, cause oxidative stress and inflammation. In this review we discuss the potential role of PKR in metabolic syndrome, pathways activated by it and the…interrelationship between pathways activated, modes of propagation if one of the pathways is inhibited or activated. Specific and effective inhibitors of PKR are being developed and can become potential treatment for metabolic syndrome and prevent many diseases.
Abstract: Red blood cells (RBCs) exhibit a unique deformability, which enables them to change shape reversibly in response to an external force. The deformability of RBCs allows them to flow in microvessels while transporting oxygen and carbon dioxide. In this review, we discussed the major determinants of RBC deformability, which include cell geometry, internal viscosity, rheological properties of the membrane, osmotic pressure, calcium, nitric oxide, temperature, ageing, and depletion of adenosine triphosphate. Additionally, we highlighted the various methods and techniques used to measure RBC deformability. Individual cell analyses (pipette aspiration and optical tweezers) and bulk cell analyses (ektacytometry, multiple channels) were…described and compared. Finally, we reviewed the correlation between RBC deformability and clinical outcomes such as diabetic microangiopathy.
Abstract: The properties, structure and functions of the erythrocyte or red blood cell (RBC) have been known and evaluated by using simpler to more sophisticated technical devices. Microscopy, flow cytometry, spectrometry, spectroflurometry, aggregometer, ektacytometer zeta potential, amperometry, electrophoresis and centrifugation, are apparatus used to qualitatively and quantitatively characterize RBC, based on the principles of light transmission, light scattering spectroscopy, light absorption, fluorescence, light polarization, shear stress, shear rate, charge and molecular weight gradients. There is a symbiosis between the chemical, the physical and the mechanical principles of those instrumental analysis and the RBC properties to be measured. Here we briefly exemplify…the relationship between the biochemical, biophysical and mechanical based techniques and the properties of the erythrocyte in healthy and disease.
Abstract: Genome engineering, or alternatively called ‘genome editing,’ has been one of the rapidly growing fields of biotechnology for the last few decades. Scientists are now making targeted modifications of genome in any organism of choice with improved precision. In this mini review, we provide basic, fundamental theory and mechanisms of the well-known genome editing technologies such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 system. We also discuss its role in the field of genetic research and highlight its therapeutic potential as an indispensable tool for the development of personalized medicine…to come in near future.
Abstract: Celecoxib (CLX) delivery and its enzyme-sensitive release from Inulin-d-alfa-tocopherol succinate (INVITE) nanomicelles are the main goals of this paper. CLX is a highly hydrophobic drug belonging to BCS class II (low solubility, high permeability). For this reason its formulation is problematic and its biopharmaceutical performances strongly depend from the applied delivery system. In the last years, INVITE nanomicelles has been shown their potential in the delivery of highly hydrophobic drugs such as curcumin and for this reason have been chosen as a good candidate for CLX delivery. Furthermore, due to the presence of ester bonds between INU and VITE it…has been supposed that the drug release could show enzyme-sensitive (esterase) behaviors. Thus CLX was loaded in INVITE nanomicelles, the loading was quantified and the physical stability was evaluated up to 90 days, finally, drug release studies in the presence or in the absence of the specific enzyme esterase were performed.
Keywords: Inulin, Vitamin E, celecoxib, micelles, drug delivery, esterase
Abstract: Stenoses in arterial blood vessels by artherosclerotic processes can decrease the supply of downstream tissue dramatically. The implantation of stents by percutaneous coronary intervention is one method of choice to restore the physiological blood flow. In some cases in-stent re-stenoses by thrombotic events, vascular wall hyperplasia or endothelial dysfunction occur. Causes and nature underlying this processes are not fully understood. Aim of the present study was to study the re-stenotic processes after stent impress on a cellular and molecular level in vitro . Therefore, human arterial endothelial cells (HUAEC) were seeded on a model vascular wall intima consisting of…extracellular matrix secreted by bovine corneal endothelial cells. Subsequently, a pre-mounted balloon-expendable tubular stent made of 316 L was impressed through the HUAEC layer leading to an impairment of the vessel wall intima. After stent removal the wound healing process, HUAEC membrane integrity, vitality, proliferation and function were assessed. Immediately after stent impress an increased level of lactate dehydrogenase (LDH) was observed indicating an impairment of the cell membrane integrity. After 24 h baseline LDH values presented again. HUAEC vitality adjacent to the stent impress induced wound was normal (investigated by inverted microscopy). The proliferation of HUAEC was the highest in the direct vicinity of the stent impress induced wound. Prostacyclin and nitric oxide decreased significantly indicating a temporary loss of cell function. These results could imply that the healing process of the endothelial cell lesion is superior to the maintenance of vascular tonicity and downregulation of platelet aggregation.
Keywords: Endothelial cells, stent impression, in vitro study