Cell Metabolic Behavior Research Articles

Data-driven parameterization and development of mechanistic cell cultivation models in monoclonal antibody production processes: Shifts in cell metabolic behavior

Representative kinetic models to describe monoclonal antibody (mAb) production processes are needed for effective process design. The development of mechanistic models can be impeded by the lack of complete understanding of changes in cell metabolism, e.g., lactate metabolic shifts. State-estimation-based methods were applied to assess the fit of available kinetic models over experimental runs. The results indicated the regions where model parameter updates were required. Different clustering strategies were applied to isolate the variations in the culture environment and correlate them to the lactate shifts. Alternative formulations for the specific lactate consumption/production term were provided for each identified phase. Two case studies are presented for pilot-scale data in different reactor types. The results show the improvement in modeling accuracy and highlight the role of oxygen and nutrient levels on the shifts. The approach showcases the use of data-driven insights to effectively utilize limited experimental data to develop robust mechanistic models.

Special Issue on “Frontiers in Connecting Steady-State and Dynamic Approaches for Modelling Cell Metabolic Behavior”

Understanding the behaviour of cell metabolism is the crucial key in bioprocess development and optimization, as well as in the development of efficient therapies [...]

Research progress on effect of magnetic nanoparticle composite scaffold on osteogenesis.

Magnetic nanoparticles (MNP) have been widely used as biomaterials due to their unique magnetic responsiveness and biocompatibility, which also can promote osteogenic differentiation through their inherent micro-magnetic field. The MNP composite scaffold retains its superparamagnetism, which has good physical, mechanical and biological properties with significant osteogenic effects and . Magnetic field has been proved to promote bone tissue repair by affecting cell metabolic behavior. MNP composite scaffolds under magnetic field can synergically promote bone tissue repair and regeneration, which has great application potential in the field of bone tissue engineering. This article summarizes the performance of magnetic composite scaffold, the research progress on the effect of MNP composite scaffold with magnetic fields on osteogenesis, to provide reference for further research and clinical application.

Recent Advances of Magnetic Nanomaterials in Bone Tissue Repair.

The magnetic field has been proven to enhance bone tissue repair by affecting cell metabolic behavior. Magnetic nanoparticles are used as biomaterials due to their unique magnetic properties and good biocompatibility. Through endocytosis, entering the cell makes it easier to affect the physiological function of the cell. Once the magnetic particles are exposed to an external magnetic field, they will be rapidly magnetized. The magnetic particles and the magnetic field work together to enhance the effectiveness of their bone tissue repair treatment. This article reviews the common synthesis methods, the mechanism, and application of magnetic nanomaterials in the field of bone tissue repair.

A kinetic metabolic study of lipid production in Chlorella protothecoides under heterotrophic condition

BackgroundMicroalgae have been proposed as potential platform to produce lipid-derived products, such as biofuels. Knowledge on the intracellular carbon flow distribution may identify key metabolic processes during lipid synthesis thus refining culture/genetic strategies to maximize cell lipid productivity. A kinetic metabolic model simulating cell metabolic behavior and lipid production was first applied in the microalgae platform Chlorella protothecoides under heterotrophic condition. It combines both physiology and flux information in a kinetic approach. Cell nutrition, growth, lipid production and almost 30 metabolic intermediates covering central carbon metabolism were included and simulated.ResultsModel simulations were shown to adequately agree with experimental data, which is suggesting that the proposed model copes with Chlorella protothecoides cells’ biology. The dynamic metabolic flux analysis using the model showed a reversible starch flux from accumulation to decomposing when glucose reached depletion, while net lipid flux shows a quasi-constant rate. The sensitive flux parameters on starch and lipid metabolism suggested that starch synthesis is the major competing pathway that affects lipid accumulation in C. protothecoides. Flux analysis also demonstrated that high lipid yield under heterotrophic condition is accompanied with high lipid flux and low TCA activity. Meanwhile, the dynamic flux distribution also suggests a relatively constant ratio of glucose distributed to biomass, lipid, starch, nucleotides as well as pentose phosphate pathway.ConclusionThe model described not only experimental data, but also unraveled intracellular carbon flow distribution and identify key metabolic processes during lipid synthesis. Most of the metabolic kinetics also showed statistical significance for metabolic mechanism. Therefore, this study unravels the mechanisms of the glucose impact on the dynamic carbon flux distribution, thus improving our understanding of the links between carbon fluxes and lipid metabolism in C. protothecoides.

Useful Tips, Widely Used Techniques, and Quantifying Cell Metabolic Behavior.

The insect cell culture/baculovirus system has three primary applications: (1) recombinant protein synthesis, (2) biopesticide synthesis, and (3) as a model system (e.g., for studying apoptosis). The fundamental techniques involved in these applications are described throughout this book. In this chapter the most widely used techniques are summarized and the reader is directed to detailed information found elsewhere in this book. Furthermore, many useful tips and my personal preferences that are rarely published are discussed in this chapter along with quantitative methods to characterize cell growth, baculovirus infection, and metabolism.

Toward a Spatially-Resolved Model of Metabolism in Dense Bacterial Colonies

An individual cell's metabolic behavior is dependent on several factors, including both its protein-expression state as well as the availability of nutrients in its local environment. These two factors are not always independent; several transcription and translational regulatory systems allow the cell to respond to changes in its environment by adjusting the expression of metabolic enzymes, and thereby shifting its usage among different substrates. By integrating two methods for modeling whole cell phenomena, namely time-dependent reaction-diffusion master equation (RDME) sampling and steady-state flux-balance analysis (FBA), we are able to study how the competition for resources among bacteria in a dense colony gives rise to local micro-environments, and how these micro-environments in turn give rise to drastically different metabolic behaviors among cells. We find, in particular, that cooperative behavior can emerge among cells within the colony. Cells in the anaerobic interior of the colony partially metabolize glucose to acetate, which can then be taken up and metabolized by cells on the more aerobic periphery of the colony.

Diagnostic and prognostic application of positron emission tomography in breast imaging: emerging uses and the role of PET in monitoring treatment response

Positron emission tomography (PET) is an imaging modality that using radiotracers, permits real-time dynamic monitoring of biologic processes such as cell metabolic behavior and proliferation, and has proven useful as a research tool for understanding tumor biology. While it does not have a well-defined role in breast cancer for the purposes of screening, diagnosis, or prognosis, emerging PET technologies and uses could expand the applications of PET in breast cancer. Positron emission mammography may provide an alternative adjunct imaging modality for the screening and diagnosis of high-risk patients unable to tolerate MRI. The development of radiotracers with the ability to measure hormonal activity could provide a non-invasive way to assess hormone receptor status and functionality. Finally, the role of PET technologies in monitoring early treatment response may prove particularly useful to research involving new therapeutic interventions.

Analysis of Single Cell Metabolic Behavior in Controlled and High throughput Microfluidic Culture Array

The metabolic factor supply influences the cellular response. We have found based on bulk experiment that mouse embryonic stem (mES) cells have higher proliferation rates under lower metabolic factor supply while human carcinoma cells proliferate faster under higher metabolic factor supply. In terms of mES cells, the differentiation shows distinguished patterns of cell lines under different metabolic factor concentrations. These show the important role of extra-cellular metabolic factors on the fundamental modulation of cell growth and transcript gene expression. Single cell analysis shows the variation of individual cell response which could better demonstrate the true cellular phenomenon rather than the bulk experiments. However, which the conventional cell culture, the concentration effect cannot be addressed on a single cell level though the entire culture period, as well as the precise and time-dependent control of input doses, the immediate cellular responses cannot be obtained. Here we have developed a high throughput microfluidic chip for single cell trapping and long term culture with refined control of perfusions, which enables various data collection for the statistical trend of cell population upon metabolic gradient and variation of individual cells’ gene expression. With this microchip, we are able to capture isolated single cells in 70 % of 1.2K chambers, and provide various metabolic gradients with refined control of the concentration and rate, perfusion time and intervals. With the convenient time-lapse observation of fluorescence probes addressing the mitochondria metabolic rate and observation of proliferation, we are able to quantitatively address the immediate response of cells as well as their long term behavior in regard of concentration effects on a single cell level.

Investigation of NS0 cell metabolic behavior in monoclonal antibody producing clones.

Investigation of NS0 cell metabolic behavior in monoclonal antibody producing clones.

An Autoradiographic Study of <sup>3</sup>H-Proline Utilization by Aging Mouse Skeletal Tissues

Autoradiographic data of <sup>3</sup>H-proline turnover by mouse skeletal cell compartments of different age were subjected to graphical analysis for the further characterization of the effects of age on skeletal cell metabolic behavior. Periosteal osteoblasts showed early significant age changes by 26 weeks of age, paralleling the previously reported histocytomorphological changes. Age changes appeared to be nonsignificant in metaphyseal osteoblasts at 52 weeks of age, however, the total turnover of <sup>3</sup>H-proline was adjusted to the reduced functional demands associated with trabecular remodeling and closure of the epiphyseal plate. The dramatic changes observed in <sup>3</sup>H-proline uptake and turnover of the epiphyseal plate cartilage cells coincided with the closure of the plate and termination of matrix formation. In addition, highly significant age changes occurred in response to the cessation of functional demands. Residual articular cartilage cells appeared to be capable of retaining their viability, staving off early age changes, thus insuring a reasonably healthy joint function in older animals. The effects of age on the skeletal cell utilization of <sup>3</sup>H-proline were best expressed as a series of steady-state events of diminishing activity. The time table for significant age changes varied in different cell compartments and also in similar cell types located at different anatomical sites. Modulation of the time table for skeletal cell aging appeared to be dictated by functional demands.