Large-scale cell production of stem cells for clinical application using the automated cell processing machine

Abstract

BackgroundCell-based regeneration therapies have great potential for application in new areas in clinical medicine, although some obstacles still remain to be overcome for a wide range of clinical applications. One major impediment is the difficulty in large-scale production of cells of interest with reproducibility. Current protocols of cell therapy require a time-consuming and laborious manual process. To solve this problem, we focused on the robotics of an automated and high-throughput cell culture system. Automated robotic cultivation of stem or progenitor cells in clinical trials has not been reported till date. The system AutoCulture® used in this study can automatically replace the culture medium, centrifuge cells, split cells, and take photographs for morphological assessment. We examined the feasibility of this system in a clinical setting.ResultsWe observed similar characteristics by both the culture methods in terms of the growth rate, gene expression profile, cell surface profile by fluorescence-activated cell sorting, surface glycan profile, and genomic DNA stability. These results indicate that AutoCulture® is a feasible method for the cultivation of human cells for regenerative medicine.ConclusionsAn automated cell-processing machine will play important roles in cell therapy and have widespread use from application in multicenter trials to provision of off-the-shelf cell products.

Comparison of manual and automated cultures of bone marrow stromal cells for bone tissue engineering

“…For example, manual and automated cell cultures of cardiac stem cells were directly compared with respect to cell growth rate, gene expression, cell surface profiles, and genomic DNA stability (8). However, most of those studies used automated culture systems that simply replaced the human procedure with robotics.…”

“…To date, several automated cell culture systems have become commercially available (8e11), such as Auto Culture (Kawasaki Heavy Industries) (8) and CompacT SelecT (The Automation Partnership) (9e11), in which cells are cultured using open culture vessels manipulated by robotic arms incorporated into the aseptically controlled chamber. Because the robotic arm can replicate manual operations, this type of system has broad applicability for various types of cells.…”

Designing a blueprint for next‐generation stem cell bioprocessing development

“…Furthermore, advances in technologies and informatic tools for generating and processing massive biological datasets will require contributions from a myriad of fields from basic research to stem cell bioprocessing. These required contributions include the development of rapid run time or real‐time measurements as well as techniques for data‐based modeling and control of bioprocessing (Kami et al, ; Manzoni et al, ; Wu & Zhou, ). Design of integrated bioprocesses: an integrated approach for the design of entire bioprocesses would recognize the interactions outlined above, and enable new bioprocessing design methods to take these into considerations. Bioprocess engineering fundamentals, including culture design, bioreactor development, and process automation, must be combined with cellular system biology principles to guide the development of next‐generation technologies and tools to produce hPSC‐derived products in a robust, cost‐effective manner (Lei, Jeong, Xiao, & Schaffer, ; Wu & Zhou, ).…”

Scalable 96-well Plate Based iPSC Culture and Production Using a Robotic Liquid Handling System

“…These issues limit the predictability and speed at which newly generated stem cell lines can be cultured in suspension. Others have developed robotic plate handling systems that mimic plate culture techniques 30,31 but these platforms demand significant investments for equipment and expertise to operate in addition to the fundamental challenges associated with stem cell culture.…”