Prediction of antibody production performance change in Chinese hamster ovary cells using morphological profiling.

Monoclonal antibodies (mAbs) represent a significant segment of biopharmaceuticals, with the market for mAb therapeutics expected to reach $200 billion in 2021. Chinese Hamster Ovary (CHO) cells are the industry standard for large-scale mAb production owing to their adaptability and genetic engineering capabilities. However, maintaining consistent product quality is challenging, primarily because of the inherent genetic instability of CHO cells. In this study, we address the need for advanced technologies for quality monitoring of host cells in biopharmaceuticals. We highlight the limitations of traditional cell assessment techniques such as flow cytometry and propose a noninvasive, label-free image-based analysis method. By utilizing advanced image processing and machine learning, this technique aims to non-invasively and quantitatively evaluate subtle quality changes in suspension cells. The research aims to investigate the use of morphological analysis for identifying subtle alterations in mAb productivity of CHO cells, employing cells stimulated by compounds as a model for this study. Our results show that the mAb productivity of CHO cells (day 8) can be predicted only from their early morphological profile (day 3). Our study also discusses the importance of strategic methods for forecasting host cell mAb productivity using morphological profiles, as inferred from our machine learning models specialized in predictive score prediction and anomaly prediction.

In Vitro Model of Human Skeletal Muscle Tissues with Contractility Fabricated by Immortalized Human Myogenic Cells.

In the development process for drugs used to treat skeletal muscle, cell-based contractile force assays have been considered as a useful in vitro test. Immortalized human myogenic cells are promising as cell sources for reproducible and well-characterized in vitro models. In this study, it is investigated whether immortalized human myogenic cells, Hu5/KD3, have suitable contractile ability and the potential to be used as cell sources for contractile force assays. Muscle tissues are fabricated using Hu5/KD3 cells on the microfabricated devices used to measure contractile force. The tissues generate a tetanic force of ≈30 µN in response to the electrical pulse stimulation (EPS). Gene expression analysis of the myosin heavy chain (MYH) isoform indicates that the tissues mostly consisted of muscle fibers expressing MYH7 or/and MYH8. The addition of dexamethasone or lovastatin decreases the contractile force of the tissues, indicating that the tissues have the potential to evaluate drug candidates designed to treat muscle atrophy or statin-induced myopathy. It is also demonstrated that the contractile force of tissues increased when EPS is applied as an artificial exercise. These results indicate that the Hu5/KD3 tissues can be employed for contractile force assays and would be useful for in vitro human skeletal muscle models.