Robotic high-throughput biomanufacturing and functional differentiation of human pluripotent stem cells

Efficient translation of human induced pluripotent stem cells (hiPSCs) requires scalable cell manufacturing strategies for optimal self renewal and functional differentiation. Traditional manual cell culture is variable and labor intensive, posing challenges for high throughput applications. Here, we established a robotic platform and automated all essential steps of hiPSC culture and differentiation under chemically defined conditions. This approach allowed rapid and standardized manufacturing of billions of hiPSCs that can be produced in parallel from up to 90 different patient-and disease-specific cell lines. Moreover, we established automated multi-lineage differentiation and generated functional neurons, cardiomyocytes, and hepatocytes. To validate our approach, we compared robotic and manual cell culture operations and performed comprehensive molecular and cellular characterizations (e.g., single-cell transcriptomics, mass cytometry, metabolism, electrophysiology) to benchmark industrial-scale cell culture operations toward building an integrated platform for efficient cell manufacturing for disease modeling, drug screening, and cell therapy.

Automated summary

Efficient translation of human induced pluripotent stem cells (hiPSCs) into scalable cell manufacturing strategies was achieved through the establishment of a robotic platform. Automated essential steps of hiPSC culture and differentiation were conducted under chemically defined conditions. The approach enabled rapid and standardized production of billions of hiPSCs from various patient-and disease-specific cell lines, as well as automated multi-lineage differentiation into functional neurons, cardiomyocytes, and hepatocytes. Comprehensive molecular and cellular characterizations were performed to validate the robotic cell culture operations and benchmark industrial-scale cell culture for disease modeling, drug screening, and cell therapy.