Automated Cell Expansion: Trends & Outlook of Critical Technologies

Abstract

Cell therapy products (CTP) are set to experience a surge in demand by the mass market in the coming decade. Automation is expected to play a key role in meeting this demand. In this review, we summarize the features of current automated cell expansion systems and highlight some of the trends and promising developments. The focuses of current systems are enabling scalability, maintaining sterility, eliminating contamination and controlling quality. To attain full automation of CTP manufacturing, several challenges have to be overcome. We identify challenges pertaining to scalability via sterile reconnections, direct cell measurements for cell-specific quality control, logistical issues in traceability, temperature control during transport, as well as administrative burden of regulations. Ultimately, automation would ensure product quality and repeatability at a lower labor cost.

Identification of senescent cells in multipotent mesenchymal stromal cell cultures: Current methods and future directions

“…For example, dynamic-culture bioreactors or planar-culture 'cell factories' [91][92][93][94], which may ultimately dictate the method employed. So far, the senescence status of MSCs grown on microcarriers in bioreactors continues to be assessed off-line [22] following MSC harvesting, plating in 2D and SA--gal activity staining in monolayer conditions [95]. Off-line here refers to monitoring by sampling a small volume of the cell culture for further analysis, either beside or away from the manufacturing line.…”

“…Off-line here refers to monitoring by sampling a small volume of the cell culture for further analysis, either beside or away from the manufacturing line. Comparatively, on-line methods require no sampling and provide realtime information of the cells' environment [22].…”

“…Therefore, the assessment of MSC cultures for the presence of senescent cells may become one of the critical quality attributes (CQAs) [21] helping to ensure the best MSC product quality. This review article presents current methods for MSC senescence analysis, and highlights promising new methods that are non-destructive and label-free with potential to become on-line [22] quality control tests [23] for therapeutic MSC products.…”

Microfluidic Sensing System with a Multichannel Surface Plasmon Resonance Chip: Damage-Free Characterization of Cells by Pattern Recognition

“…With the remarkable development in stem-cell and genome-editing technologies, , cell culture systems for models to understand, diagnose, and treat diseases have received increasing attention as an alternative to conventional animal experiments . Recent advances in three-dimensional culturing, microfluidic technologies (so-called organ-on-a-chip), and high-throughput automated cell culture systems − are paving the way for the use of cultured cells for industrial applications. While such technologies to control cell culture have grown rapidly, there still remain issues associated with assessing cells in culture.…”

A Microfluidic Sensing System with a Multichannel Surface Plasmon Resonance Chip: Damage-free Characterization of Cells by Pattern Recognition

“…With the remarkable development in stem-cell-and genome-editing technologies, cell culture systems for models to understand, diagnose, and treat diseases have received increasing attention as an alternative to conventional animal experiments. 1 Recent advances in three-dimensional culturing, 2 microfluidic technologies (so-called organ-on-a-chip), 3 and high-throughput automated cell culture systems 4 are paving the way for the use of cultured cells for industrial applications. While such technologies to control cell culture have grown rapidly, there still remain issues associated with assessing cells in culture.…”