Adherent Cell Culture Platform: Tailor To Achieve Your Research Objectives & Scale Requirements | Corning

The following content was originally published by Cell & Gene Therapy Insights on November 4, 2022.

The cell and gene therapy field is rapidly advancing, placing a focus on manufacturing challenges to meet the growing demand. The efficient harvest of viable cells or cell products and maintenance of native biological function influences platform and workflow choices. Established protocols for viral vector production on a range of scalable adherent platforms can be tailored to meet end objectives, taking into consideration factors such as desired yield, time to optimize the process, facility space, and media usage. Essentially, there is no ‘one-size-fits-all’ platform for upstream adherent cell culture.

Solutions for Upstream Adherent Cell Culture

Corning offers manufacturing-ready platform solutions for upstream adherent cell culture allowing use for a diverse range of applications (Table 1). The platforms each offer different advantages and disadvantages, meaning they should be matched to your research or manufacturing objectives. Planar vessels such as Corning® CellSTACK® chambers, HYPERStack® vessels, and CellCube® modules are scalable, modular platforms that can be easily integrated into modular production setups, with available automation. In addition, the Corning Ascent® FBR (Fixed Bed Reactor) System is a closed-circulation system with process control designed to provide high-yield, and viable cell recovery. The process development scale system available now is scalable from 1–5 m2. Pilot and Production scale Ascent FBR systems in development will scale from 20–1,000 m2 for largescale production. Microcarriers have multiple surface options, including Corning CellBIND® surface treatment, to tailor the surface to the specific cell type and application. When cultured in a bioreactor, the process control and scalability of a suspension platform can be achieved.

Scale-up of MSCs With High Viability, Multipotency Markers

Mesenchymal stem cells (MSCs) from several sources were expanded on the Corning CellBIND CellCube 25-layer module and the HYPERSTACK 36-layer vessel (Table 2). Human bone marrow, adipose, and umbilical cord-derived MSCs exhibit high viability, high density, cell expansion on the Corning CellBIND surface across multiple planar vessels with comparable yields on each platform tested. MSCs retain >99% expression of CD90/CD105/CD7, <0.5% hematopoietic lineage markers.

Scalable Viral Vector Production by Transient Transfection

Vector yield from transient production systems can be improved with process optimization and transfection design of experiment (DoE). Comparable productivity of adeno-associated virus (AAV) (GC/cm2) was found on both the traditional planar Corning HYPERStack 12-layer vessel and the Corning Ascent FBR system (Figure 1). Either platform could be used as a suitable method for AAV vector production, dependent on customer needs. Higher infectious lentiviral (LV) titer yield (TU/cm2) was achieved with Corning HYPER technology as the unique, gas-permeable surface provides favorable conditions for cell growth and LV packaging. 

Conclusion

Choosing an adherent cell culture platform is a complex balance between several factors, including experimental objectives and desired scale.