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the effect of green and black tea polyphenols on brca2 deficient chinese hamster cells by synthetic lethality through parp inhibition.tea polyphenols are known antioxidants presenting health benefits due to their observed cellular activities. in this study, two tea polyphenols, epigallocatechin gallate, which is common in green tea, and theaflavin, which is common in black tea, were investigated for their parp inhibitory activity and selective cytotoxicity to brca2 mutated cells. the observed cytotoxicity of these polyphenols to brca2 deficient cells is believed to be a result of parp inhibition induced synthetic lethality. ch ...201930875717
virus removal filtration of chemically defined chinese hamster ovary cells medium with nanocellulose-based size exclusion filter.sterility of bioreactors in biotherapeutic processing remains a significant challenge. virus removal size-exclusion filtration is a robust and highly efficient approach to remove viruses. this article investigates the virus removal capacity of nanocellulose-based filter for upstream bioprocessing of chemically defined chinese hamster ovary (cho) cells medium containing pluronic f-68 (powercho™, lonza) and supplemented with insulin-transferrin-selenium (its) at varying process parameters. virus r ...201930871931
host-antibody inductivity of virulent entamoeba histolytica and non-virulent entamoeba moshkovskii in a mouse model.despite similarities in morphology, gene and protein profiles, entamoeba histolytica and e. moshkovskii show profound differences in pathogenicity. entamoeba histolytica infection might result in amoebic dysentery and liver abscess, while e. moshkovskii causes only mild diarrhea. extensive studies focus on roles of host immune responses to the pathogenic e. histolytica; however, evidence for e. moshkovskii remains scarce.201930867040
a novel led-based 2d-fluorescence spectroscopy system for in-line bioprocess monitoring of chinese hamster ovary cell cultivations-part ii.this study was performed in order to evaluate a new led-based 2d-fluorescence spectrometer for in-line bioprocess monitoring of chinese hamster ovary (cho) cell culture processes. the new spectrometer used selected excitation wavelengths of 280, 365, and 455 nm to collect spectral data from six 10-l fed-batch processes. the technique provides data on various fluorescent compounds from the cultivation medium as well as from cell metabolism. in addition, scattered light offers information about th ...201932625013
both irradiated and bystander effects link with dna repair capacity and the linear energy transfer.in comparison with a low linear energy transfer (let) radiation, a high-let radiation induces more complex dna damage. this study wonders whether radiation-induced bystander effect (ribe) is dependent of let.201930858123
selection of vaccinia virus-neutralizing antibody from a phage-display human-antibody library.although smallpox was eradicated in 1980, it is still considered a potential agent of biowarfare and bioterrorism. smallpox has the potential for high mortality rates along with a major public health impact, eventually causing public panic and social disruption. passive administration of neutralizing monoclonal antibodies (mabs) is an effective intervention for various adverse reactions caused by vaccination and the unpredictable nature of emerging and bioterrorist-related infections. currently, ...201930856707
secreting oviduct epithelial cells of coturnix coturnix japonica (qoec) and changes to their proteome after nonviral transfection.the quail oviduct (coturnix c. japonica) is a natural candidate avian bioreactor, while the secretive quail oviduct epithelial cells (qoecs) are potential in vitro producers of recombinant proteins and vaccines. in view of the need for highly performing and transformable cell lines, qoec may potentially act as an alternative bioreactor platform to the existing ones, for example, to the chinese hamster ovary. the aim of this work was to characterize qoecs and their response to nucleofection with ...201930854717
transient manipulation of the expression level of selected growth rate correlating micrornas does not increase growth rate in cho-k1 cells.engineering of chinese hamster ovary cells by manipulating microrna (mirna) expression levels has been shown to induce advantageous, desired phenotypes. most of these studies so far were concerned with increasing productivity or reducing growth rate (with the implied intention of thus freeing cellular resources to also increase productivity). here we evaluated the ability of growth correlating mirnas to increase the growth rate of cho-k1 cells by transient overexpression or knock down, respectiv ...201930853633
rapid establishment of stable retroviral packaging cells and recombinant susceptible target cell lines employing novel transposon vectors derived from sleeping beauty.viral vector particles derived from murine leukemia virus (mlv) mediate highly efficient stable gene transfer used in gene therapeutic approaches and in the generation of transgenic cell lines. however, the establishment of stable viral packaging cells (vpcs) is a time-consuming challenge. to overcome this limitation, we successfully generated novel sleeping beauty-derived transposon vectors entailing envelope and packaging expression cassettes as well as a transfer vector. upon multiplexed tran ...201930852270
metabolic engineering of chinese hamster ovary cells towards reduced biosynthesis and accumulation of novel growth inhibitors in fed-batch cultures.chinese hamster ovary (cho) cells in fed-batch cultures are known to consume large amounts of nutrients and divert significant portion of them towards the formation of byproducts, some of which, including lactate and ammonia, are known to be growth inhibitory in nature. a major fraction of these inhibitory metabolites are byproducts or intermediates of amino acid catabolism. limiting the supply of amino acids has been shown to curtail the production of corresponding inhibitory byproducts resulti ...201930851381
chemical, cytotoxic and genotoxic analysis of etidronate in sodium hypochlorite solution.to test whether the incorporation of a chelation powder, etidronate, marketed for root canal irrigation (dual rinse hedp) into a sodium hypochlorite (naocl) solution induced additional cytotoxic and genotoxic effects not observed with naocl alone.201930848496
in vitro and in vivo evaluation of 6-o-α-maltosyl-β-cyclodextrin as a potential therapeutic agent against niemann-pick disease type c.niemann-pick disease type c (npc) is a rare lysosomal storage disease characterized by the dysfunction of intracellular cholesterol trafficking with progressive neurodegeneration and hepatomegaly. we evaluated the potential of 6-o-α-maltosyl-β-cyclodextrin (g2-β-cd) as a drug candidate against npc. the physicochemical properties of g2-β-cd as an injectable agent were assessed, and molecular interactions between g2-β-cd and free cholesterol were studied by solubility analysis and two-dimensional ...201930845767
crispr/cas9 targeted capture of mammalian genomic regions for characterization by ngs.the robust detection of structural variants in mammalian genomes remains a challenge. it is particularly difficult in the case of genetically unstable chinese hamster ovary (cho) cell lines with only draft genome assemblies available. we explore the potential of the crispr/cas9 system for the targeted capture of genomic loci containing integrated vectors in cho-k1-based cell lines followed by next generation sequencing (ngs), and compare it to popular target-enrichment sequencing methods and to ...201930837529
induction of peripheral lymph node addressin in human nasal mucosa with eosinophilic chronic rhinosinusitis.eosinophilic chronic rhinosinusitis (ecrs) is characterised by formation of nasal polyps with prominent eosinophilic infiltration; however, how eosinophils are recruited in this pathological setting remains unclear. in the present study, we carried out quantitative immunohistochemical analysis of nasal polyps associated with ecrs (n=30) and non-ecrs (n=30) to evaluate expression of an l-selectin ligand peripheral lymph node addressin (pnad) on vascular endothelial cells. we found that pnad was i ...201930837082
site-specific roles of n-linked oligosaccharides in recombinant eel follicle-stimulating hormone for secretion and signal transduction.eel follicle-stimulating hormone (eelfsh) is composed of a common α-subunit and a hormone specific β-subunit, both of which contain two n-linked carbohydrate residues. we characterized the biologically active single chains by fusing the α-subunit to the carboxyl terminal region of the eelfsh β-subunit. expression vectors were constructed and the biological activity of the recombinant hormones (rec-hormones) was characterized using chinese hamster ovary (cho) k1 cells expressing the eelfsh recept ...201930836102
electrophysiological and pharmacological characterization of human inwardly rectifying kir2.1 channels on an automated patch-clamp platform.inwardly rectifying ik1 potassium currents of the heart control the resting membrane potential of ventricular cardiomyocytes during diastole and contribute to their repolarization after each action potential. mutations in the gene encoding kir2.1 channels, which primarily conduct ventricular ik1, are associated with inheritable forms of arrhythmias and sudden cardiac death. therefore, potential iatrogenic inhibition of kir2.1-mediated ik1 currents is a cardiosafety concern during new drug discov ...201930835490
evaluation of pertussis toxin expression in b2 and thijs media.whole-cell pertussis vaccine (wp) has been imperative and highly effective in preventing childhood deaths due to pertussis. pertussis toxin is one of the virulence factors of bordetella pertussis in all available pertussis vaccines. wp production in razi vaccine and serum research institute is according to bioreactor culture of b. pertussis strains in b2 medium. the aim of this study was to evaluate b. pertussis strain 509 pt production in b2 and thalen-ijssel (thijs) media by chinese hamster ov ...201931013007
establishment of a monoclonal antibody pmab-225 against alpaca podoplanin for immunohistochemical analyses.podoplanin (pdpn) is known as a lymphatic endothelial cell marker. monoclonal antibodies (mabs) against human, mouse, rat, rabbit, dog, cat, bovine, pig, and horse pdpn have been established in our previous studies. however, mabs against alpaca pdpn (apdpn), required for immunohistochemical analysis, remain to be developed. in the present study, we employed the cell-based immunization and screening (cbis) method for producing anti-apdpn mabs. we immunized mice with apdpn-overexpressing chinese h ...201930997422
predicting the cytotoxicity of disinfection by-products to chinese hamster ovary by using linear quantitative structure-activity relationship models.a suitable model to predict the toxicity of current and continuously emerging disinfection by-products (dbps) is needed. this study aims to establish a reliable model for predicting the cytotoxicity of dbps to chinese hamster ovary (cho) cells. we collected the cho cytotoxicity data of 74 dbps as the endpoint to build linear quantitative structure-activity relationship (qsar) models. the linear models were developed by using multiple linear regression (mlr). the mlr models showed high performanc ...201930989598
development of a long-acting fc-fused cocaine hydrolase with improved yield of protein expression.human butyrylcholinesterase (bche) is known as a safe and effective protein for detoxification of organophosphorus (op) nerve agents. its rationally designed mutants with considerably improved catalytic activity against cocaine, known as cocaine hydrolases (cochs), are recognized as the most promising drug candidates for the treatment of cocaine abuse. however, it is a grand challenge to efficiently produce active recombinant bche and cochs with a sufficiently long biological half-life. in the p ...201930986387
application of the bradford assay for cell lysis quantification: residual protein content in cell culture supernatants.frequently measured mammalian cell culture process indicators include viability and total cell concentration (tcc). cell lysis, an additional important process characteristic that substantially contributes to the overall product purity profiles, is often not addressed in detail. in the present study, an inexpensive and simple application of the bradford assay is developed to determine the residual protein content (rpc) in cell culture supernatants. the reliability and reproducibility of the meth ...201930983130
three consecutive pregnancies in a patient with chronic autoimmune thyroid disease associated with hypothyroidism and extremely high levels of anti-thyrotropin receptor antibodies.background: thyroid-stimulating hormone (tsh) receptor (tshr) antibodies (trab) can be present in chronic autoimmune thyroiditis. transplacental trab transfer can lead to fetal thyroid dysfunction and serious complications. patient findings: we report the case of a woman with autoimmune hypothyroidism and extremely high trab levels, with blocking and stimulating activities (biological activities characterized with chinese hamster ovary cells expressing tshr). at week 22 of her first pregnancy, s ...201930973063
anxa2- and ctsd-knockout cho cell lines to diminish the risk of contamination with host cell proteins.chinese hamster ovary (cho) cells have been used as host cells in the production of a range of recombinant therapeutic proteins, including monoclonal antibodies and fc-fusion proteins. host cell proteins (hcp) represent impurities that must be removed from therapeutic formulations because of their potential risks for immunogenicity. while the majority of hcp impurities are effectively removed in typical downstream purification processes, clearance of a small population of hcp remains challenging ...201930972970
a combined cell-free protein synthesis and fluorescence-based approach to investigate gpcr binding properties.fluorescent labeling of de novo synthesized proteins is in particular a valuable tool for functional and structural studies of membrane proteins. in this context, we present two methods for the site-specific fluorescent labeling of difficult-to-express membrane proteins in combination with cell-free protein synthesis. the cell-free protein synthesis system is based on chinese hamster ovary cells (cho) since this system contains endogenous membrane structures derived from the endoplasmic reticulu ...201930969411
genetic and epigenetic variation across genes involved in energy metabolism and mitochondria of chinese hamster ovary cell lines.the increasingdemandfor biopharmaceutical products drives the search for efficient cell factories that are able to sustainably support rapid growth, high productivity, and product quality. as these depend on energy generation, here the genomic variation in nuclear genes associated with mitochondria and energy metabolism and the mitochondrial genome of 14 cell lines is investigated. the variants called enable reliable tracing of lineages. unique sequence variations are observed in cell lines adap ...201930969017
targeted capture of chinese hamster ovary host cell proteins: peptide ligand discovery.the growing integration of quality-by-design (qbd) concepts in biomanufacturing calls for a detailed and quantitative knowledge of the profile of impurities and their impact on the product safety and efficacy. particularly valuable is the determination of the residual level of host cell proteins (hcps) secreted, together with the product of interest, by the recombinant cells utilized for production. though often referred to as a single impurity, hcps comprise a variety of species with diverse ab ...201930965558
hydrophobic amines and their guanidine analogues modulate activation and desensitization of asic3.acid-sensing ion channel 3 (asic3) is an important member of the acid-sensing ion channels family, which is widely expressed in the peripheral nervous system and contributes to pain sensation. asics are targeted by various drugs and toxins. however, mechanisms and structural determinants of ligands' action on asic3 are not completely understood. in the present work we studied asic3 modulation by a series of "hydrophobic monoamines" and their guanidine analogs, which were previously characterized ...201930959896
identification of consensus sequence from matrix attachment regions and functional analysis of its activity in stably transfected chinese hamster ovary cells.matrix attachment regions (mars) can enhance transgene expression levels and maintain stability. however, the consensus sequence from mars and its functional analysis remains to be examined. here, we assessed a possible consensus sequence from mars and assessed its activity in stably transfected chinese hamster ovary (cho) cells. first, we analyzed the effects of 10 mars on transfected cho cells and then analyzed the consensus motifs from these mars using a bioinformatics method. the consensus s ...201930957285
human genome-derived top1 matrix attachment region enhances transgene expression in the transfected cho cells.to investigate the effect of full-length fragment of dna topoisomerase i gene (top1) matrix attachment regions (mars) originating from the human genome on transgene expression in chinese hamster ovary (cho) cells and explore the underlying mechanisms.201930953310
a novel led-based 2d-fluorescence spectroscopy system for in-line monitoring of chinese hamster ovary cell cultivations - part i.a new two-dimensional fluorescence sensor system was developed for in-line monitoring of mammalian cell cultures. fluorescence spectroscopy allows for the detection and quantification of naturally occurring intra- and extracellular fluorophores in the cell broth. the fluorescence signals correlate to the cells' current redox state and other relevant process parameters. cell culture pretests with twelve different excitation wavelengths showed that only three wavelengths account for a vast majorit ...201932625014
use of virus-like particles as a native membrane model to study the interaction of insulin with the insulin receptor.there is emerging evidence of the utility of virus-like particles (vlps) as a novel model for the study of receptor-ligand interactions in a native plasma membrane environment. vlps consist of a viral core protein encapsulated by portions of the cell membrane with membrane proteins and receptors expressed in their native conformation. vlps can be generated in mammalian cells by transfection with the retroviral core protein (gag). in this study, we used chinese hamster ovary (cho t10) cells stabl ...201930951702
nanodiamond/poly-ε-caprolactone nanofibrous scaffold for wound management.we describe preparation, characterization and cytocompatibility of nanodiamond (nd) dispersed in poly (ε-caprolactone) (pcl) based nanofibrous scaffold. the results show that this unique scaffold potentially provides essential properties for wound healing by enhancing proliferation of epithelial cells, in addition to restricting the microbial activities. electrospinning technique was used to fabricate and develop pcl-nds nanocomposite scaffold. the developed nanocomposites were characterized for ...201930948073
escherichia coli bmp-2 showed comparable osteoinductivity with chinese hamster ovary derived bmp-2 with demineralized bone matrix as carrier.escherichia coli bone morphogenetic protein-2 (erhbmp-2) had a larger yield but less osteoinductivity than chinese hamster ovary cell bone morphogenetic protein-2 (crhbmp-2). since the release profile of rhbmp-2 affects its osteoinductivity, an appropriate carrier could improve the effect of erhbmp-2. demineralized bone matrix (dbm) was one of the most widely used bone substitutes, but few studies evaluated the osteoinductivity of erhbmp-2 while it was carried by dbm. therefore, we compared the ...201930947586
exploring isoxazoles and pyrrolidinones decorated with the 4,6-dimethoxy-1,3,5-triazine unit as human farnesyltransferase inhibitors.unprecedented triazinyl-isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2-ethynyl-4,6-dimethoxy-1,3,5-triazine as dipolarophile. the biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine-isoxazole moieties. the replacement of the isoxazole unit by a pyrrolidin-2-one was detrimental to the inhibitory activity while the p ...201930947375
risk assessment of heterogeneous tio2-based engineered nanoparticles (nps): a qstr approach using simple periodic table based descriptors.nowadays, the risk assessment of engineered nanoparticles (nps) on human health and animals is of great importance. we have used here simple periodic table based descriptors for mixture compounds to predict the cytotoxicity for the heterogeneous nps. we have developed mono parametric quantitative structure-toxicity relationship (qstr) models for 34 tio2-based nps modified with (poly) metallic clusters of noble metals (au, ag, pt) to assess the cytotoxicity (-log ec50) towards chinese hamster ova ...201930938199
revisiting the mechanism of enfuvirtide and designing an analog with improved fusion inhibitory activity by targeting triple sites in gp41.to revisit the mechanism of action of enfuvirtide (t20) and based on the newly defined mechanism, design an analogous peptide of t20 with improved antiviral activity.201930932963
from nutritional wealth to autophagy: in vivo metabolic dynamics in the cytosol, mitochondrion and shuttles of igg producing cho cells.to fulfil the optimization needs of current biopharmaceutical processes the knowledge how to improve cell specific productivities is of outmost importance. this requires a detailed understanding of cellular metabolism on a subcellular level inside compartments such as cytosol and mitochondrion. using igg1 producing chinese hamster ovary (cho) cells, a pioneering protocol for compartment-specific metabolome analysis was applied. various production-like growth conditions ranging from ample glucose ...201930930288
recombinant human erythropoietin proteins synthesized in escherichia coli cells: effects of additional domains on the in vitro and in vivo activities.the aim of this work was to compare biological activities of three variants of bacterially expressed human recombinant erythropoietin (epo) with additional protein domains: 6his-s-tag-epo protein carrying the s-tag (15-a.a. oligopeptide from bovine pancreatic ribonuclease a) at the n-terminus and hbd-epo and epo-hbd proteins containing heparin-binding protein domains (hbd) of the bone morphogenetic protein 2 from danio rerio at the n- and c-termini, respectively. the commercial preparation epost ...201930927522
application of imaging flow cytometry for the characterization of intracellular attributes in chinese hamster ovary cell lines at the single-cell level.biopharmaceutical manufacturing using chinese hamster ovary (cho) cells requires the generation of high-producing clonal cell lines. during cell line development, cell cloning using fluorescence-activated cell sorting (facs) has the potential to combine isolation of single cells with sorting based on specific cellular attributes that correlate with productivity and/or growth, identifying cell lines with desirable phenotypes for manufacturing. this study describes the application of imaging flow ...201930925020
simultaneous detection of nicotinamide adenine nucleotides and adenylate pool to quantify redox and energy states in mab-producing cho cells by capillary electrophoresis.chinese hamster ovary (cho) cells are predominant in the production of therapeutic proteins to treat various diseases. characterization and investigation of cho cell metabolism in a quick and simple way could boost process and cell line development. therefore, a method to simultaneously detect seven redox- and energy-related metabolites in cho cells by capillary electrophoresis has been developed. an on-line focusing technique was applied to improve the peak shape and resolution by using a 50 μm ...201930923861
crispr/cas9 as a genome editing tool for targeted gene integration in cho cells.the emergence of crispr/cas9 system as a precise and affordable method for genome editing has prompted its rapid adoption for the targeted integration of transgenes in chinese hamster ovary (cho) cells. targeted gene integration allows the generation of stable cell lines with a controlled and predictable behavior, which is an important feature for the rational design of cell factories aimed at the large-scale production of recombinant proteins. here we present the protocol for crispr/cas9-mediat ...201930912048
enhancing expression level and stability of transgene mediated by episomal vector via buffering dna methyltransferase in transfected cho cells.nonviral episomal vectors present attractive alternative vehicles for gene therapy applications. previously, we have established a new type of nonviral episomal vector-mediated by the characteristic motifs of matrix attachment regions (mars), which is driven by the cytomegalovirus (cmv) promoter. however, the cmv promoter is intrinsically susceptible to silencing, resulting in declined productivity during long-term culture. in this study, chinese hamster ovary (cho) cells and dna methyltransfera ...201931074065
usnic acid attenuates genomic instability in chinese hamster ovary (cho) cells as well as chemical-induced preneoplastic lesions in rat colon.usnic acid (ua) is one of the pharmacologically most important compounds produced by several lichen species. to better understand the mechanism of action (moa) of this important substance, this study examined the genotoxicity attributed to ua and its influence on mutagens with varying moa using the micronucleus (mn) test in chinese hamster ovary cells (cho). additional experiments were conducted to investigate the effect of ua on colon carcinogenesis in wistar rats employing the aberrant crypt f ...201931066341
multi-omics profiling of cho parental hosts reveals cell line-specific variations in bioprocessing traits.chinese hamster ovary (cho) cells are the most prevalent mammalian cell factories for producing recombinant therapeutic proteins due to their ability to synthesize human-like post-translational modifications and ease of maintenance in suspension cultures. currently, a wide variety of cho host cell lines has been developed; substantial differences exist in their phenotypes even when transfected with the same target vector. however, relatively less is known about the influence of their inherited g ...201931066037
forecasting and control of lactate bifurcation in chinese hamster ovary cell culture processes.biomanufacturing exhibits inherent variability that can lead to variation in performance attributes and batch failure. to help ensure process consistency and product quality the development of predictive models and integrated control strategies is a promising approach. in this study, a feedback controller was developed to limit excessive lactate production, a widespread metabolic phenomenon that is negatively associated with culture performance and product quality. the controller was developed b ...201931062870
characterization of intact glycopeptides reveals the impact of culture media on site-specific glycosylation of epo-fc fusion protein generated by cho-gs cells.with the increasing demand to provide more detailed quality attributes, more sophisticated glycan analysis tools are highly desirable for biopharmaceutical manufacturing. here, we performed an intact glycopeptide analysis method to simultaneously analyze the site-specific n- and o-glycan profiles of the recombinant erythropoietin fc (epo-fc) protein secreted from a chinese hamster ovary glutamine synthetase stable cell line and compared the effects of two commercial culture media, ex-cell (ex) a ...201931062865
all-optical crosstalk-free manipulation and readout of chronos-expressing neurons.all optical neurophysiology allows manipulation and readout of neural network activity with single-cell spatial resolution and millisecond temporal resolution. neurons can be made to express proteins that actuate transmembrane currents upon light absorption, enabling optical control of membrane potential and action potential signalling. in addition, neurons can be genetically or synthetically labelled with fluorescent reporters of changes in intracellular calcium concentration or membrane potent ...201931057183
insights into the loss of protein sialylation in an fc-fusion protein-producing cho cell bioprocess.sialylation affects circulating half-life, charge distribution, and other biochemical properties of therapeutic glycoproteins. loss of protein sialylation during glycoprotein-producing bioprocesses could lead to a low final protein sialylation level and bring negative effects on subsequent clinical efficacy. in this work, an fc-fusion protein-producing chinese hamster ovary cell fed-batch culture process was studied and insights into the loss of protein sialylation during the fc-fusion protein p ...201931049620
attenuated glutamine synthetase as a selection marker in cho cells to efficiently isolate highly productive stable cells for the production of antibodies and other biologics.chinese hamster ovary (cho) cells are the biopharmaceutical industry's primary means of manufacturing therapeutic proteins, including monoclonal antibodies. the major challenge in cell line development for the production of recombinant biopharmaceuticals lies in generating and isolating rare high-producing stable clones, amongst thousands of low-producing or unstable clones, in a short period of time. one approach to accomplish this is to use the glutamine synthetase (gs) selection system, toget ...201931043114
the glycosylation design space for recombinant lysosomal replacement enzymes produced in cho cells.lysosomal replacement enzymes are essential therapeutic options for rare congenital lysosomal enzyme deficiencies, but enzymes in clinical use are only partially effective due to short circulatory half-life and inefficient biodistribution. replacement enzymes are primarily taken up by cell surface glycan receptors, and glycan structures influence uptake, biodistribution, and circulation time. it has not been possible to design and systematically study effects of different glycan features. here w ...201931040271
direct and indirect effects of exposure to 900 mhz gsm radiofrequency electromagnetic fields on cho cell line: evidence of bystander effect by non-ionizing radiation.the rapid rise in global concerns about the adverse health effects of exposure to radiofrequency radiation (rfr) generated by common devices such as mobile phones has prompted scientists to further investigate the biological effects of these environmental exposures. non-targeted effects (ntes) are responses which do not need a direct exposure to be expressed and are particularly significant at low energy radiations. although ntes of ionizing radiation are well documented, there are scarcely any ...201931036329
ouabain enhances cell-cell adhesion mediated by β1 subunits of the na+,k+-atpase in cho fibroblasts.adhesion is a crucial characteristic of epithelial cells to form barriers to pathogens and toxic substances from the environment. epithelial cells attach to each other using intercellular junctions on the lateral membrane, including tight and adherent junctions, as well as the na+,k+-atpase. our group has shown that non-adherent chinese hamster ovary (cho) cells transfected with the canine β1 subunit become adhesive, and those homotypic interactions amongst β1 subunits of the na+,k+-atpase occur ...201931035668
the less the better: how suppressed base addition boosts production of monoclonal antibodies with chinese hamster ovary cells.biopharmaceutical production processes strive for the optimization of economic efficiency. among others, the maximization of volumetric productivity is a key criterion. typical parameters such as partial pressure of co2 (pco2) and ph are known to influence the performance although reasons are not yet fully elucidated. in this study the effects of pco2 and ph shifts on the phenotypic performance were linked to metabolic and energetic changes. short peak performance of qmab (23 pg/cell/day) was ac ...201931032253
establishment of dhfr-deficient hek293 cells for high yield of therapeutic glycoproteins.since the use of protein therapeutics is effective for treating intractable human diseases, the production of biologic therapeutic agents has dramatically increased over the past three decades. the chinese hamster ovary (cho) cell lines are the most commonly used host cell expression system for recombinant protein production. high productive and stable clonal cell lines for recombinant protein production have been established from the dhfr-deficient cho cell using the dihydrofolate reductase/met ...201931031194
transcription factor engineering in cho cells for recombinant protein production.the continuous increase of approved biopharmaceutical products drives the development of more efficient recombinant protein expression systems. chinese hamster ovary (cho) cells are the mainstay for this purpose but have some drawbacks, such as low levels of expression. several strategies have been applied to increase the productivity of cho cells with different outcomes. transcription factor (tf) engineering has emerged as an interesting and successful approach, as these proteins can act as mas ...201931030575
phenotypic characterization of a novel type 2 diabetes animal model in a shanxi mu colony of chinese hamsters.developing animal models for human diseases is critical for studying complex diseases such as type 2 diabetes mellitus (t2dm). since inbred colonies of chinese hamsters tend toward spontaneous development of diabetes, we investigated them as a possible model.201931025261
proteogenomic annotation of chinese hamsters reveals extensive novel translation events and endogenous retroviral elements.a high-quality genome annotation greatly facilitates successful cell line engineering. standard draft genome annotation pipelines are based largely on de novo gene prediction, homology, and rna-seq data. however, draft annotations can suffer from incorrect predictions of translated sequence, inaccurate splice isoforms, and missing genes. here, we generated a draft annotation for the newly assembled chinese hamster genome and used rna-seq, proteomics, and ribo-seq to experimentally annotate the g ...201931020842
improvements in single-use bioreactor film material composition leads to robust and reliable chinese hamster ovary cell performance.single-use technologies, in particular disposable bioreactor bags, have become integral within the biopharmaceutical community. however, safety concerns arose upon the identification of toxic leachable compounds derived from the plastic materials. although the leachable bis(2,4-di-tert-butylphenyl)-phosphate (bdtbpp) has been previously shown to inhibit cho cell growth, it is critical to determine if other compounds like this are still present in subsequent generations of films for industrial ap ...201931017345
incorporation of an intramolecular hydrogen bonding motif in the side chain of antimalarial benzimidazoles.analogues of a novel class of benzimidazoles with an intramolecular hydrogen bonding motif have been synthesized and evaluated in vitro for their antiplasmodium activity against chloroquine-sensitive (nf54) and multi-drug resistant (k1) strains of the human malaria parasite plasmodium falciparum. compounds were also screened for their cytotoxicity towards a mammalian chinese hamster ovarian (cho) cell line. most of the compounds exhibited good antiplasmodium activity (pfnf54 ic50 <1 μm) and were ...201931015908
synthesis and characterization of porous structures of rutile tio2 /na0.8ti4o8/na2ti6o13 for biomedical applications.this method involves the use of molding, pressing and sintering techniques applied to different powder mixtures of tio2 with sodium bicarbonate nahco3 (15 wt% and 30 wt% nahco3), to obtain porous structures of rutile tio2/na0.8ti4o8/na2ti6o13 and na0.8ti4o8/na2ti6o13 for possible biomedical implant applications. the method validation includes x-ray diffraction patterns (xrd) analysis refined by the rietveld method using x'pert highscore plus. the surface morphology was observed by using a scanni ...201931193424
tcnst2 encodes a golgi-localized udp-galactose transporter in trypanosoma cruzi.survival and infectivity of trypanosomatids rely on cell-surface and secreted glycoconjugates, many of which contain a variable number of galactose residues. incorporation of galactose to proteins and lipids occurs along the secretory pathway from udp-galactose (udp-gal). before being used in glycosylation reactions, however, this activated sugar donor must first be transported across the endoplasmic reticulum and golgi membranes by a specific nucleotide sugar transporter (nst). in this study, w ...201931190664
insight into the roles of tyrosine on rcho cell performance in fed-batch cultures.tyrosine (tyr), as one of the least soluble amino acids, is essential to monoclonal antibody (mab) production in recombinant chinese hamster ovary (rcho) cell cultures since its roles on maintaining the specific productivity (qmab) and avoiding tyr sequence variants. to understand the effects of tyr on cell performance and its underlying mechanisms, rcho cell-producing mabs were cultivated at various cumulative tyr addition concentrations (0.6 to 5.5 mm) in fed-batch processes. low tyr concentra ...201931190239
genotoxicity evaluation of a phragmitis rhizoma extract using a standard battery of in vitro and in vivo assays.a rhizome of phragmites communis trinius has been used in traditional medicine to remove a heat, relieve vomiting and fever, nourish body fluids, and treat diseases like cancers. however, the safety of phragmitis rhizoma has not yet been fully assessed.201931189082
a new heparan sulfate from the mollusk nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of plasmodium falciparum.despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of plasmodium falciparum-infected erythrocytes (pf-ies).201931188952
metabolomic profiling of cho fed-batch growth phases at 10, 100, and 1,000 l.established bioprocess monitoring is based on quick and reliable methods, including cell count and viability measurement, extracellular metabolite measurement, and the measurement of physicochemical qualities of the cultivation medium. these methods are sufficient for monitoring of process performance, but rarely give insight into the actual physiological states of the cell culture. however, understanding of the latter is essential for optimization of bioprocess development. our study used lc-ms ...201931184374
site-specific phosphorylation of villin remodels the actin cytoskeleton to regulate sendai viral glycoprotein-mediated membrane fusion.connivance of cellular factors during virus-host cell membrane fusion is poorly understood. we have recently shown that cellular villin plays an important role during membrane fusion of reconstituted sendai virosomes with hepatocytes. here, we employed villin-null chinese hamster ovary (cho) cells, where villin expression led to an increased fusion with virosomes, which was further enhanced due to tyrosine phosphorylation in the presence of c-src. however, the villin rri mutant, lacking actin-se ...201931183850
reduction of il-2 fragmentation during manufacturing of a novel immunocytokine by doe process optimization.interleukin-2 (il-2) is a potent molecule in cancer therapy. clinical application, however, is limited due to its strong side effects during the treatment. we developed an il-2 variant (il-2v) immunocytokine to circumvent the drawbacks of the current il-2 therapy. during the production of the il-2v immunocytokine in chinese hamster ovary (cho) cells, molecules with fragmented il-2v and therefore reduced cytokine activity can be observed. to control product fragmentation different production proc ...201931180133
impact of mammalian cell culture conditions on monoclonal antibody charge heterogeneity: an accessory monitoring tool for process development.recombinant monoclonal antibodies are predominantly produced in mammalian cell culture bioprocesses. post-translational modifications affect the micro-heterogeneity of the product and thereby influence important quality attributes, such as stability, solubility, pharmacodynamics and pharmacokinetics. the analysis of the surface charge distribution of monoclonal antibodies provides aggregated information about these modifications. in this work, we established a direct injection ph gradient cation ...201931175523
differential effects of bioreactor process variables and purification on the human recombinant lysosomal enzyme β-glucuronidase produced from chinese hamster ovary cells.β-glucuronidase is a lysosomal enzyme and a molecular model of a class of therapeutics approved as enzyme replacement therapies for lysosomal storage diseases. understanding the effect of bioreactor process variables on the production and quality of the biologics is critical for maintaining quality and efficacy of the biotherapeutics. here, we have investigated the effect of three process variables, in a head-to-head comparison using a parallel bioreactor system (n = 8), namely 0.25 mm butyrate ...201931175430
novel short synthetic matrix attachment region for enhancing transgenic expression in recombinant chinese hamster ovary cells.matrix attachment regions (mars) are dna fragments with specific motifs that enhance transgenic expression; however, the characteristics and functions of these elements remain unclear. in this study, we designed and synthesized three short chimeric mars, namely, sm4, sm5, and sm6, with different numbers and orders of motifs on the basis of the features and motifs of previously reported mars, namely, sm1, sm2, and sm3, respectively. expression vectors with six synthetic mars flanking the down or ...201931168866
characterization of a gdp-fucose transporter and a fucosyltransferase involved in the fucosylation of glycoproteins in the diatom phaeodactylum tricornutum.although phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation. for example, incorporation of fucose residues in the glycans n-linked to protein in p. tricornutum is questionable. indeed, such epitope has previously been found on n-glycans of endogenous glycoproteins in p. tricornutum. meanwhile, ...201931164895
screening naturally occurring phenolic antioxidants for their suitability as additives to cho cell culture media used to produce monoclonal antibodies.this study identified several antioxidants that could be used in chinese hamster ovary (cho)cell culture media and benefit monoclonal antibody production. the flavan-3-ols, catechin, epicatechin, epigallocatechin gallate and gallocatechin gallate all had no detrimental effect on cell viability at the concentrations tested, and they reduced the final viable cell count with a resulting rise in the cell specific productivity. the flavone, luteolin behave similarly to the flavan-3-ols. resveratrol a ...201931163664
genotoxicity evaluation of tobacco and nicotine delivery products: part two. in vitro micronucleus assay.in this study, a variety of test matrices from tobacco and nicotine delivery products were assessed against a 3r4f kentucky reference cigarette using the in vitro micronucleus assay. testing was conducted using two chinese hamster cell lines (cho and v79), and a human lymphoblastoid cell line (tk6), in accordance with established guidelines. total particulate matter (tpm) from a 3r4f reference cigarette was compared to an electronic cigarette e-liquid, electronic cigarette tpm and tpm from a com ...201931163219
establishment of an anticetacean podoplanin monoclonal antibody pmab-237 for immunohistochemical analysis.podoplanin (pdpn) has been utilized as a lymphatic endothelial cell marker especially in pathological diagnoses. therefore, sensitive and specific monoclonal antibodies (mabs) targeting pdpn are needed for immunohistochemical analyses using formalin-fixed paraffin-embedded tissues. recently, anti-pdpn mabs against many species, such as human, mouse, rat, rabbit, dog, cat, bovine, pig, and horse were established in our studies. however, anticetacean (whale) pdpn (wpdpn) has not been established y ...201931161965
bip inducer x: an er stress inhibitor for enhancing recombinant antibody production in cho cell culture.prolonged endoplasmic reticulum (er) stress reduces protein synthesis and induces apoptosis in mammalian cells. when dimethyl sulfoxide (dmso), a specific monoclonal antibody productivity (qmab )-enhancing reagent, is added to recombinant chinese hamster ovary (rcho) cell cultures (gsr cell line), it induces er stress and apoptosis in a dose-dependent manner. to determine an effective er stress inhibitor, three er stress inhibitors (bip inducer x [bix], tauroursodeoxycholic acid, and carbazole) ...201931161665
development of an improved lentiviral based vector system for the stable expression of monoclonal antibody in cho cells.therapeutic monoclonal antibodies (mabs) have become the dominant products in biopharmaceutical industry. mammalian cell expression systems including chinese hamster ovary (cho) cells are the most commonly used hosts for the production of complex recombinant proteins. however, development of stable, high producing cho cell lines suffers from the low expression level and instability of the transgene. the increasing efforts in the development of novel therapeutic antibodies and the advent of biosi ...201931156045
cation exchange chromatography performed in overloaded mode is effective in removing viruses during the manufacturing of monoclonal antibodies.viral safety is a critical concern with regard to monoclonal antibody (mab) products produced in mammalian cells such as chinese hamster ovary cells. manufacturers are required to ensure the safety of such products by validating the clearance of viruses in downstream purification steps. cation exchange (cex) chromatography is widely used in bind/elute mode as a polishing step in mab purification. however, bind/elute modes require a large volume of expensive resin. to reduce the production cost, ...201931148380
superfluous glutamine synthetase activity in chinese hamster ovary cells selected under glutamine limitation is growth limiting in glutamine-replete conditions and can be inhibited by serine.passaging and expansion of animal cells in lean maintenance medium could result in periods of limitation of some nutrients. over time, such stresses could possibly result in selection of cells with metabolic changes and contribute to heterogeneity. here, we investigate whether selection of chinese hamster ovary (cho) cells under glutamine limitation results in changes in growth under glutamine-replete conditions. in glutamine-limiting medium, compared to control cells passaged in glutamine-rich ...201931148368
immune persistence 17 to 20 years after primary vaccination with recombination hepatitis b vaccine (cho) and the effect of booster dose vaccination.to assess the immune persistence conferred by a chinese hamster ovary (cho)-derived hepatitis b vaccine (hepb) 17 to 20 years after primary immunization during early life.201931146699
precision of scoring radiation-induced chromosomal aberrations and micronuclei by unexperienced scorers.purpose: dose assessment plays an important role in case of radiological accidents and can be performed by scoring structural changes of chromosome morphology induced in cells by ionizing radiation. the results of such a test are biased by scorer experience, therefore, simple to learn assays are recommended to be used when fast analysis of a large amount of data is needed. the aim of this study was to compare the performance of two radiobiological assays - chromosomal aberrations and micronuclei ...201931140900
oxidative stress and endoreduplication induced by blue light exposure to cho cells.blue light is commonly used for the treatment of neonatal jaundice and as a photodynamic therapy for cancer. in comparison to ultraviolet light, blue light has a lower toxicity due to the differences in photon energies. however, blue light can still be mutagenic to cells. the proposed mechanism suggests blue light exposure induces reactive oxygen species inducing oxidative stress. in this study, we examined how blue light exposure caused genotoxic effects utilizing chinese hamster ovary (cho) ce ...201931138408
evaluation of a single amino acid substitution at position 79 of human ifn-α2b in interferon-receptor assembly and activity.type i interferons (ifns) are homologous cytokines that bind to a cell surface receptor and establish signaling pathways that motivate immune responses. the purpose of the current study is to assess the activity of a novel-engineered ifn-α2b. the crystallographic structure of ifn-α2b and its receptors was acquired from protein data bank. various amino acid substitutions were designed based on structural properties and other biological characteristics of residues to find the most effective amino ...201931135267
comparative toxicity study of a novel non-ionic surfactant, vanillin ethoxylates, and nonylphenol ethoxylates in chinese hamster ovary cells in vitro.surfactants such as alkylphenol polyethoxylates (apeos) and nonylphenol ethoxylates (npeos) are commonly used worldwide, but the majority of these compounds, together with their metabolites, have been reported to induce severe biological toxicity. here, we evaluated for the first time the cytotoxicity, genotoxicity and mitochondrial damage in chinese hamster ovary (cho-k1) cells caused by a novel non-ionic surfactant, vanillin ethoxylates (vaeos), an alternative to apeos. in parallel, the same i ...201931133271
photochemical oxidation of ppcps using a combination of solar irradiation and free available chlorine.the degradation of pharmaceuticals and personal care products (ppcps) by using solar photolysis in the presence of free available chlorine (fac) was investigated in simulated drinking water. the combination of free available chlorine and sunlight irradiation dramatically accelerated the degradation of all the contaminants tested through the generation of hydroxyl radicals, reactive chlorine species (rcs) and ozone. contaminants containing electron-donating moieties degraded quickly and were pref ...201931129545
a flipr assay for discovery of gabaa receptor modulators of natural origin.a fluorometric imaging plate reader (flipr) assay utilizing chinese hamster ovary (cho) cells stably transfected with gabaa receptors of α1β2γ2 subunit composition was evaluated and validated for rapid screening of plant extract libraries and efficient localization of active compounds in extracts. validation was performed with pure compounds and extracts known to contain allosteric gabaa receptor modulators. plants extracts that had been previously reported as active in an assay using xenopus la ...201931127604
in vitro cytotoxicity studies of industrial eucalyptus kraft lignins on mouse hepatoma, melanoma and chinese hamster ovary cells.kraft lignin is a polyphenolic compound generated as a by-product from the kraft pulping process in large quantities annually worldwide. in addition to its commercial availability, its structural features make it worth to be considered in the pharmaceutical area. the present study was carried out to evaluate in vitro antioxidant and cytotoxic properties of kraft lignin on mouse hepatoma mh-22a, melanoma b16 (tumor cells) and chinese hamster ovary (cho, non-cancerous) cells. moreover, several ana ...201931125648
application of er stress biomarkers to predict formulated monoclonal antibody stability.for a therapeutic monoclonal antibody (mab) to reach the clinic, the molecule must be produced at an appropriate yield and quality, then formulated to maintain efficacy and stability. the formation of subvisible particles (svps) can impact product stability and is monitored during formulation development; however, the potential of a mab to form such species can be influenced throughout the whole bioprocess. the levels of intracellular endoplasmic reticulum (er) stress perceived by chinese hamste ...201931119893
multiple conserved elements structuring inverted repeats in the mammalian coat color-related gene asip.in the agouti signaling gene protein (asip) of the house mouse (mus musculus), inverted repeat (ir) arrays are known to exist in a non-coding region adjacent to the ventral-specific promoter region and the accompanying two exons (exons 1a and 1a'), which are around 100 kb upstream from the amino acid coding regions of exons 2, 3, and 4. to determine the gene structure of mammalian asip and to elucidate trends in its evolution, non-coding sequences of six rodent (mouse, rat, chinese hamster, squi ...201931116535
improvement of growth rates through nucleoside media supplementation of cho clones.chinese hamster ovary (cho) cells are used for the production of therapeutic proteins. this work examines improving passaging growth rate of two cho clones. growth rates were significantly improved for both clones with supplementation of the nucleosides cytidine, hypoxanthine, uridine, and thymidine to the culturing media at the optimal concentration of 100 µm of each nucleoside. we investigated supplementing the same combination of nucleosides to seed bioreactors and production fed batch biorea ...201931115721
improved recombinant protein production by regulation of transcription and protein transport in chinese hamster ovary cells.to identify genes that affected protein expression in chinese hamster ovary (cho) cells was significant, and we identified the changes in the transcriptome and the functional gene sets that would contribute to increase expression of recombinant protein.201931114947
small-molecule control of antibody n-glycosylation in engineered mammalian cells.n-linked glycosylation in monoclonal antibodies (mabs) is crucial for structural and functional properties of mab therapeutics, including stability, pharmacokinetics, safety and clinical efficacy. the biopharmaceutical industry currently lacks tools to precisely control n-glycosylation levels during mab production. in this study, we engineered chinese hamster ovary cells with synthetic genetic circuits to tune n-glycosylation of a stably expressed igg. we knocked out two key glycosyltransferase ...201931110306
purification and analytics of a monoclonal antibody from chinese hamster ovary cells using an automated microbioreactor system.monoclonal antibodies (mabs) are one of the most popular and well-characterized biological products manufactured today. most commonly produced using chinese hamster ovary (cho) cells, culture and process conditions must be optimized to maximize antibody titers and achieve target quality profiles. typically, this optimization uses automated microscale bioreactors (15 ml) to screen multiple process conditions in parallel. optimization criteria include culture performance and the critical quality a ...201931107445
ca2+ signal is involved in endothelin-1-induced internalization of endothelin type a receptor expressed in chinese hamster ovary cells.endothelin type a receptor (etar) is internalized upon agonist stimulation; however, the mechanism thereof remains controversial. in this study, we characterized the endothelin-1 (et-1)-induced internalization of etar expressed in chinese hamster ovary cells. et-1 elicited etar internalization and increase in intracellular ca2+ concentration. et-1-induced etar internalization was completely inhibited by a reduction in intracellular and extracellular ca2+ levels and partially suppressed by inhibi ...201931103330
comparative toxicity of organic mixture attached to road deposited sediments: inadequacy of conventionally using individual pollutants to assess comprehensive hazard effects.organic pollutants attached on road deposited sediments (rds) during dry days can be washed-off into stormwater runoff during rainfall events, undermining stormwater reuse safety. previous research studies commonly utilized individual pollutant groups and their quantity to evaluate the hazard effect of pollutants attached to rds in terms of stormwater reuse. since many types of organic pollutants are present together rather than individually, conventional approaches might not permit a comprehens ...201931102843
limiting the metabolic burden of recombinant protein expression during selection yields pools with higher expression levels.in order to avoid the metabolic burden of protein expression during cell growth, and to avoid potential toxicity of recombinant proteins, microbial expression systems typically utilize regulated expression vectors. in contrast, constitutive expression vectors have usually been utilized for isolation of protein expressing mammalian cell lines. in mammalian systems, inducible expression vectors are typically utilized for only those proteins that are toxic when overexpressed. we developed a tetracy ...201931090257
identification and crispr/cas9 inactivation of the c1s protease responsible for proteolysis of recombinant proteins produced in cho cells.proteolysis associated with recombinant protein expression in chinese hamster ovary (cho) cells has hindered the development of biologics including hiv vaccines. when expressed in cho cells, the recombinant hiv envelope protein, gp120, undergoes proteolytic clipping by a serine protease at a key epitope recognized by neutralizing antibodies. the problem is particularly acute for envelope proteins from clade b viruses that represent the major genetic subtype circulating in much of the developed w ...201931087560
unstructured regions in ire1α specify bip-mediated destabilisation of the luminal domain dimer and repression of the upr.coupling of endoplasmic reticulum (er) stress to dimerisation-dependent activation of the upr transducer ire1 is incompletely understood. whilst the luminal co-chaperone erdj4 promotes a complex between the hsp70 bip and ire1's stress-sensing luminal domain (ire1ld) that favours the latter's monomeric inactive state and loss of erdj4 de-represses ire1, evidence linking these cellular and in vitro observations is presently lacking. we report that enforced loading of endogenous bip onto endogenous ...201931873072
high throughput, efficacious gene editing & genome surveillance in chinese hamster ovary cells.chinese hamster ovary (cho) cells are a common tool utilized in bioproduction and directed genome engineering of cho cells is of great interest to enhance recombinant cell lines. until recently, this focus has been challenged by a lack of efficacious, high throughput, and low-cost gene editing modalities and screening methods. in this work, we demonstrate an improved method for gene editing in cho cells using crispr rnps and characterize the endpoints of cas9 and zfn mediated genetic engineering ...201931856197
structure-effect relationships of novel semi-synthetic cannabinoid derivatives.background: as a library of cannabinoid (cb) derivatives with (-)-trans-cannabidiol (cbd) or (-)-trans-cannabidivarin (cbdv) scaffold, we synthesized nine novel cannabinoids: 2-hydroxyethyl cannabidiolate (2-hec), 2-hydroxypentyl cannabidiolate (2-hpc), 2,3-dihydroxypropyl cannabidiolate (gcbd), cyclohexyl cannabidiolate (chc), n-hexyl-cannabidiolate (hc), 2-(methylsulfonamido)ethyl cannabidiolate (nmsc), 2-hydroxyethyl cannabidivarinolate (2-hecbdv), cyclohexyl cannabidivarinolate (chcbdv), and ...201931824305
development of rolled scaffold for high-density adherent cell culture.bioreactors for large-scale culture of mammalian cells are playing vital roles in biotechnology and bioengineering. various bioreactors have been developed, but their capacity and efficiency are often limited by insufficient mass transfer rate and high shear stress. a rolled scaffold (rs) is a fully defined scaffold for high-density adherent culture of mammalian cells. the rs is a polymer film with spacers, that is rolled into a cylinder with a pre-determined gap between each turn. cells are cul ...201931813056
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