Developing an automated robotic factory for novel stem cell therapy production.

Abstract

Advanced therapeutics, specifically cell and gene therapies, provide an opportunity to target previously unmet clinical conditions and offer a potential solution to the social and economic burden associated with an aging population [1,2]. Human mesenchymal stem/stromal cells (hMSCs) are a promising cell therapy candidate for the treatment of numerous clinical indications [3]; however, a transformation is required in the way we isolate, manufacture, characterize and deliver these therapies to ensure they are both efficacious and affordable [2,4]. Manufacture of hMSCs requires in vitro expansion to increase the available number of cells to meet clinical demand; however, progress is impeded by the lack of advanced methods for the isolation and expansion of cells that are scalable, amenable for automation and closed. Many allogeneic processes still require manual intervention which has significant quality and cost implications [5], and developing reproducible, consistent bioprocesses is still a major challenge. Even when a scale-out approach is to be employed (e.g., for autologous therapies), there is a significant practical challenge of manipulating, processing and segregating multiple production batches in an aseptic, closed manner. Such processes demand small units for manufacture in which line segregation is a priority in order to avoid product–patient mismatch and disease transmission. As such, there is an industrial trend toward automated systems as it is increasingly recognized that such systems facilitate consistent manufacture and will play a pivotal role in the translation of cell therapies by improving quality control, process economics, scalability, process capability and provide a platform for understanding process variation and optimization [6]. Through AUTOSTEM (European Commission Horizon 2020 funded research and innovation actions), academic and industrial groups from across the EU are working in collaboration to take a holistic approach to enable large-scale hMSC production, at clinical-grade quality, by implementing a robotic automated pipeline for cell isolation and culture [7]. AUTOSTEM builds on the ground-breaking work of the StemCellFactory project [8] which built and demonstrated an automated robotic pipeline for the production of human induced pluripotent cell lines (Figure 1). AUTOSTEM develops this technology further to enable automated, closed and good manufacturing practice (GMP)ready hMSCs (a ‘StromalCellFactory’) and will focus on the development of: