Periodic Reporting for period 1 - MiniOrgans (An automated platform for the large-scale production of miniaturized neuromuscular organoids)
Período documentado: 2023-07-01 hasta 2024-12-31
Organoids have emerged as sophisticated 3D cell culture systems that closely mimic key aspects of in vivo tissues, providing a powerful tool to study human disease mechanisms and identify novel therapeutic strategies. These advanced models offer a unique alternative to traditional cell cultures and animal models, improving the physiological relevance of preclinical studies.
Over the past decade, significant progress has been made in stem cell and organoid research, leading to breakthroughs in disease modeling, drug discovery, and regenerative medicine. However, the field still faces critical challenges that limit the full exploitation of organoid technologies. Reproducibility and scalability remain major bottlenecks in the widespread adoption of organoids for industrial and clinical applications. The traditional manual generation of organoids is labor-intensive, time-consuming, and costly, which hinders their use in high-throughput drug screening and precision medicine. Therefore, the development of cost-effective, standardized, and automated methods for organoid production and cryopreservation is essential to bridge the gap between research and industry applications.
The objective of this project was to develop a large-scale, automated, and robust production platform for multi-organoid models derived from healthy and diseased induced pluripotent stem cell (iPSC) lines. The project focused on neuromuscular disease models, leveraging cutting-edge biomanufacturing and automation technologies to enable efficient and reproducible generation of organoids. Furthermore, we aimed to establish a proof-of-concept miniaturized organoid system for high-throughput drug screening, providing a powerful tool for pharmaceutical research.
The expected impact of this project includes:
Improved standardization and reproducibility of organoid production, making them more accessible for research and industry applications.
Reduction in animal testing, as reliable human-derived organoid models can better recapitulate disease conditions.
Acceleration of drug discovery and development through high-throughput screening approaches, enhancing the identification of promising therapeutic compounds.
Advancement toward personalized medicine, enabling patient-specific disease modeling and tailored therapeutic interventions.
Over the past decade, significant progress has been made in stem cell and organoid research, leading to breakthroughs in disease modeling, drug discovery, and regenerative medicine. However, the field still faces critical challenges that limit the full exploitation of organoid technologies. Reproducibility and scalability remain major bottlenecks in the widespread adoption of organoids for industrial and clinical applications. The traditional manual generation of organoids is labor-intensive, time-consuming, and costly, which hinders their use in high-throughput drug screening and precision medicine. Therefore, the development of cost-effective, standardized, and automated methods for organoid production and cryopreservation is essential to bridge the gap between research and industry applications.
The objective of this project was to develop a large-scale, automated, and robust production platform for multi-organoid models derived from healthy and diseased induced pluripotent stem cell (iPSC) lines. The project focused on neuromuscular disease models, leveraging cutting-edge biomanufacturing and automation technologies to enable efficient and reproducible generation of organoids. Furthermore, we aimed to establish a proof-of-concept miniaturized organoid system for high-throughput drug screening, providing a powerful tool for pharmaceutical research.
The expected impact of this project includes:
Improved standardization and reproducibility of organoid production, making them more accessible for research and industry applications.
Reduction in animal testing, as reliable human-derived organoid models can better recapitulate disease conditions.
Acceleration of drug discovery and development through high-throughput screening approaches, enhancing the identification of promising therapeutic compounds.
Advancement toward personalized medicine, enabling patient-specific disease modeling and tailored therapeutic interventions.
During the project, we successfully established and optimized an automated pipeline for large-scale organoid production using liquid handling robots. This system ensures the consistent and reproducible generation of organoids from iPSC-derived cells, reducing the variability associated with manual methods. A key achievement was the development of multi-organoid models derived from both healthy and diseased iPSC lines to study neuromuscular diseases. These models provide a relevant platform to investigate disease mechanisms and evaluate potential therapeutic interventions. Additionally, we have established a proof-of-concept paradigm of miniaturized organoids for high-throughput drug screening approaches. By scaling down the organoid size while maintaining key structural and functional properties, we enabled the application of high-throughput screening techniques to test potential drug candidates. This approach facilitates cost-effective compound screening, reducing reagent consumption and increasing assay throughput.
This project has pushed the boundaries of current organoid research by addressing key challenges related to automation, reproducibility, and high-throughput applications. While organoid technology has advanced significantly in recent years, previous approaches relied heavily on manual techniques, which introduced variability and limited scalability. Our results provide a scalable and standardized approach for integrating organoids into drug discovery pipelines, disease modeling, and regenerative medicine. This work represents a crucial step toward the industrialization of organoid technology, ultimately enabling more efficient drug development, reduced animal testing, and improved personalized treatment strategies for neuromuscular diseases and beyond.