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1.
Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection.
Heuschkel, MJ, Baumert, TF, Verrier, ER
Viruses. 2021;(8)
Abstract
Chronic hepatitis D is one of the most severe and aggressive forms of chronic viral hepatitis with a high risk of developing hepatocellular carcinoma (HCC). It results from the co-infection of the liver with the hepatitis B virus (HBV) and its satellite, the hepatitis D virus (HDV). Although current therapies can control HBV infection, no treatment that efficiently eliminates HDV is available and novel therapeutic strategies are needed. Although the HDV cycle is well described, the lack of simple experimental models has restricted the study of host-virus interactions, even if they represent relevant therapeutic targets. In the last few years, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key cellular entry factor for HBV and HDV has allowed the development of new cell culture models susceptible to HBV and HDV infection. In this review, we summarize the main in vitro model systems used for the study of HDV entry and infection, discuss their benefits and limitations and highlight perspectives for future developments.
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2.
Binary culture of microalgae as an integrated approach for enhanced biomass and metabolites productivity, wastewater treatment, and bioflocculation.
Rashid, N, Park, WK, Selvaratnam, T
Chemosphere. 2018;:67-75
Abstract
Ecological studies of microalgae have revealed their potential to co-exist in the natural environment. It provides an evidence of the symbiotic relationship of microalgae with other microorganisms. The symbiosis potential of microalgae is inherited with distinct advantages, providing a venue for their scale-up applications. The deployment of large-scale microalgae applications is limited due to the technical challenges such as slow growth rate, low metabolites yield, and high risk of biomass contamination by unwanted bacteria. However, these challenges can be overcome by exploring symbiotic potential of microalgae. In a symbiotic system, photosynthetic microalgae co-exist with bacteria, fungi, as well as heterotrophic microalgae. In this consortium, they can exchange nutrients and metabolites, transfer gene, and interact with each other through complex metabolic mechanism. Microalgae in this system, termed as a binary culture, are reported to exhibit high growth rate, enhanced bio-flocculation, and biochemical productivity without experiencing contamination. Binary culture also offers interesting applications in other biotechnological processes including bioremediation, wastewater treatment, and production of high-value metabolites. The focus of the study is to provide a perspective to enhance the understanding about microalgae binary culture. In this review, the mechanism of binary culture, its potential, and limitations are briefly discussed. A number of queries are evolved through this study, which needs to be answered by executing future research to assess the real potential of binary culture.
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3.
Hydrogel-based three-dimensional cell culture for organ-on-a-chip applications.
Lee, SH, Shim, KY, Kim, B, Sung, JH
Biotechnology progress. 2017;(3):580-589
Abstract
Recent studies have reported that three-dimensionally cultured cells have more physiologically relevant functions than two-dimensionally cultured cells. Cells are three-dimensionally surrounded by the extracellular matrix (ECM) in complex in vivo microenvironments and interact with the ECM and neighboring cells. Therefore, replicating the ECM environment is key to the successful cell culture models. Various natural and synthetic hydrogels have been used to mimic ECM environments based on their physical, chemical, and biological characteristics, such as biocompatibility, biodegradability, and biochemical functional groups. Because of these characteristics, hydrogels have been combined with microtechnologies and used in organ-on-a-chip applications to more closely recapitulate the in vivo microenvironment. Therefore, appropriate hydrogels should be selected depending on the cell types and applications. The porosity of the selected hydrogel should be controlled to facilitate the movement of nutrients and oxygen. In this review, we describe various types of hydrogels, external stimulation-based gelation of hydrogels, and control of their porosity. Then, we introduce applications of hydrogels for organ-on-a-chip. Last, we also discuss the challenges of hydrogel-based three-dimensional cell culture techniques and propose future directions. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:580-589, 2017.
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4.
Addressing Challenges to Enhance the Bioactives of Withania somnifera through Organ, Tissue, and Cell Culture Based Approaches.
Singh, P, Guleri, R, Angurala, A, Kaur, K, Kaur, K, Kaul, SC, Wadhwa, R, Pati, PK
BioMed research international. 2017;:3278494
Abstract
Withania somnifera is a highly valued medicinal plant in traditional home medicine and is known for a wide range of bioactivities. Its commercial cultivation is adversely affected by poor seed viability and germination. Infestation by various pests and pathogens, survival under unfavourable environmental conditions, narrow genetic base, and meager information regarding biosynthesis of secondary metabolites are some of the other existing challenges in the crop. Biotechnological interventions through organ, tissue, and cell culture provide promising options for addressing some of these issues. In vitro propagation facilitates conservation and sustainable utilization of the existing germplasms and broadening the genetic base. It would also provide means for efficient and rapid mass propagation of elite chemotypes and generating uniform plant material round the year for experimentation and industrial applications. The potential of in vitro cell/organ cultures for the production of therapeutically valuable compounds and their large-scale production in bioreactors has received significant attention in recent years. In vitro culture system further provides distinct advantage for studying various cellular and molecular processes leading to secondary metabolite accumulation and their regulation. Engineering plants through genetic transformation and development of hairy root culture system are powerful strategies for modulation of secondary metabolites. The present review highlights the developments and sketches current scenario in this field.
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5.
Statistical experimental designs for the production of secondary metabolites in plant cell suspension cultures.
Schmitz, C, Fritsch, L, Fischer, R, Schillberg, S, Rasche, S
Biotechnology letters. 2016;(12):2007-2014
Abstract
Statistical experimental designs, also known as the "design of experiments" (DoE) approach, are widely used to improve not only technical processes but also to answer questions in the agricultural, medical and social sciences. Although many articles have been published about the application of DoE in these fields, few studies have addressed the use of DoE in the plant sciences, particularly in the context of plant cell suspension cultures (PCSCs). Compounds derived from PCSCs can be developed as pharmaceuticals, chemical feedstocks and cosmetic ingredients, and statistical experimental designs can be used to improve the productivity of the cells and the yield and/or quality of the target compounds in a cost efficient manner. In this article, we summarize recent findings concerning the application of statistical approaches to improve the performance of PCSCs and discuss the potential future applications of this approach.
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6.
Neurodevelopmental origins of bipolar disorder: iPSC models.
O'Shea, KS, McInnis, MG
Molecular and cellular neurosciences. 2016;:63-83
Abstract
Bipolar disorder (BP) is a chronic neuropsychiatric condition characterized by pathological fluctuations in mood from mania to depression. Adoption, twin and family studies have consistently identified a significant hereditary component to BP, yet there is no clear genetic event or consistent neuropathology. BP has been suggested to have a developmental origin, although this hypothesis has been difficult to test since there are no viable neurons or glial cells to analyze, and research has relied largely on postmortem brain, behavioral and imaging studies, or has examined proxy tissues including saliva, olfactory epithelium and blood cells. Neurodevelopmental factors, particularly pathways related to nervous system development, cell migration, extracellular matrix, H3K4 methylation, and calcium signaling have been identified in large gene expression and GWAS studies as altered in BP. Recent advances in stem cell biology, particularly the ability to reprogram adult somatic tissues to a pluripotent state, now make it possible to interrogate these pathways in viable cell models. A number of induced pluripotent stem cell (iPSC) lines from BP patient and healthy control (C) individuals have been derived in several laboratories, and their ability to form cortical neurons examined. Early studies suggest differences in activity, calcium signaling, blocks to neuronal differentiation, and changes in neuronal, and possibly glial, lineage specification. Initial observations suggest that differentiation of BP patient-derived neurons to dorsal telencephalic derivatives may be impaired, possibly due to alterations in WNT, Hedgehog or Nodal pathway signaling. These investigations strongly support a developmental contribution to BP and identify novel pathways, mechanisms and opportunities for improved treatments.
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7.
Modelling atopic dermatitis during the morphogenetic process involved in reconstruction of a human epidermis.
De Vuyst, É, Mound, A, Lambert de Rouvroit, C, Poumay, Y
Current research in translational medicine. 2016;(4):179-183
Abstract
Most crucial role of epidermis is to maintain efficient barrier between the organism and its environment. This barrier is however perturbed in inflammatory skin conditions like atopic dermatitis (AD), one common chronic disease. This review depicts characteristics of a model intending to reproduce epidermal features of AD in vitro. Firstly, methyl-β-cyclodextrin (MβCD) during reconstruction of epidermis was used to deplete cholesterol from plasma membrane because this condition reproduces characteristics of AD at transcriptomic level in monolayer cultures. Major changes are confirmed after same treatment inside reconstructed human epidermis (RHE). However, since early treatment do not reveal impairment to reconstruct a functional epidermal barrier and given the importance of the Th2 dysregulated immune response in AD, cholesterol-depleted RHE at day 11 of reconstruction were then incubated with three Th2-related cytokines (IL-4, IL-13 and IL-25) previously reported as playing important roles in the development of AD, as well as altering overall function of epidermal barrier. When combining both treatments, essential epidermal features of AD are observed. Indeed, RHE then exhibit spongiosis, disappearing granular layer, alteration of barrier function, as well as dysregulated expression levels for genes involved in AD pathogenesis. Moreover, while trying to identify individual roles for each component used to create AD-like alterations, incubation with IL-4 following cholesterol depletion from plasma membrane was found inducing most of the reported alterations. This model suggests potential for better investigations of epidermal AD features and may be considered for eventual in vitro screening of cosmetics or therapeutic compounds.
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8.
Engineering parameters in bioreactor's design: a critical aspect in tissue engineering.
Salehi-Nik, N, Amoabediny, G, Pouran, B, Tabesh, H, Shokrgozar, MA, Haghighipour, N, Khatibi, N, Anisi, F, Mottaghy, K, Zandieh-Doulabi, B
BioMed research international. 2013;:762132
Abstract
Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.
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9.
Effective elicitors and process strategies for enhancement of secondary metabolite production in hairy root cultures.
Wang, JW, Wu, JY
Advances in biochemical engineering/biotechnology. 2013;:55-89
Abstract
This chapter reviews the various biotic and abiotic elicitors applied to hairy root cultures and their stimulating effects on the accumulation of secondary metabolites. Elicitors generally refer to the agents that stimulate the defense responses of plants. As a major response of plants to biotic and abiotic stress, the accumulation of secondary metabolites in plant tissue cultures can be stimulated by the elicitors. Among the many elicitors applied to hairy root cultures as well as plant cell suspension cultures, the most common and effective elicitors are fungal cell extracts, polysaccharides from fungal and plant cells, and heavy metal salts. With the crude fungal cell extracts, it is essential to observe the preparation conditions carefully for achieving reproducible effects. In addition to the chemical agents, UV-radiation, hyperosmotic stress and temperature shift have been shown effective for some plant species/metabolites. Elicitor type, dose, and treatment schedule are major factors determining the effects on the secondary metabolite production. In addition to the accumulation of products in roots, elicitor treatments often stimulate the release of intracellular products. Although elicitation is mainly effective to increase specific product yield on per unit mass of roots, the incorporation of nutrient feeding strategies can be applied to enhance the volumetric product yield. The integration of in situ product recovery from the roots/liquid medium is another synergistic strategy with the elicitor treatment to improve the process.
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10.
Hairy root culture: bioreactor design and process intensification.
Stiles, AR, Liu, CZ
Advances in biochemical engineering/biotechnology. 2013;:91-114
Abstract
The cultivation of hairy roots for the production of secondary metabolites offers numerous advantages; hairy roots have a fast growth rate, are genetically stable, and are relatively simple to maintain in phytohormone free media. Hairy roots provide a continuous source of secondary metabolites, and are useful for the production of chemicals for pharmaceuticals, cosmetics, and food additives. In order for hairy roots to be utilized on a commercial scale, it is necessary to scale-up their production. Over the last several decades, significant research has been conducted on the cultivation of hairy roots in various types of bioreactor systems. In this review, we discuss the advantages and disadvantages of various bioreactor systems, the major factors related to large-scale bioreactor cultures, process intensification technologies and overview the mathematical models and computer-aided methods that have been utilized for bioreactor design and development.