Abstract: Mesenchymal stem cells (MSCs) possess potential for differentiating into diverse cell types, offering therapeutic benefits in tissue repair and immune modulation. Despite their pluripotency and accessibility, the process of scaling-up of MSCs is laborious and time-consuming. Due to the necessity of handling a great number of vessels to provide sufficient surface area for growth, maintaining stable quality and biological activity becomes challenging.
Beyond standard static adherent cultures in multilayer vessels, novel systems have been developed for large-scale manufacturing, most of which, particularly in the context of cell harvesting, efficiency and workflow complexities are still being refined. CellFiber® is an encapsulation technology that utilizes medical-grade alginate to form a protective tubular structure providing a stable environment. This approach maximizes surface area for high-density cell culture at various scales.
This study focuses on cultivating MSCs using CellFiber technology in T75 flasks, gas permeable bags (300mL and 1000mL) and a cellbag bioreactor (2L), offering larger surface areas for adherent culture compared to traditional non-fiber cultures in the same vessels (160 cm2 with fiber versus the conventional 75cm2 in a T75 flask). Cell yields were 5.74 x 10^7 in the 1000mL gas permeable bag and 1.6 x 10^8 in the 2L cellbag bioreactor, demonstrating the feasibility of fiber culture through normal marker expression. The adjustable fiber parameters offer flexibility, enhancing the footprint efficiency and increasing the “space-effectiveness” (surface area-to-culture volume ratio). Manufacturing assumptions and cost attributes are separately outlined for further investigation of the Cost of Goods (CoGs) associated with the adoption of this innovative technology.
CellFiber® technology offers advantages in maximizing surface area within a manageable culture batch, while enabling non-enzymatic cell harvest from hydrogel fiber, thereby reducing the risk of cell loss. Preliminary results demonstrate CellFiber® benefits large-scale manufacturing with a functionally-closed workflow. This approach could serve as a compelling, cost-efficient solution to address the current challenges in MSC manufacturing processes.
