In recent years, medicine has experienced a shift towards innovative, patient-oriented therapies. Stem cells in particular are of great importance for personalized medicine and are therefore being intensively investigated. In addition, the availability of molecular biology tools such as CRISPR/Cas genome editing is opening up new possibilities. With the increasing application of patient-based cells as therapeutics or models for research, the demand for high-quality cell material is continuously growing. The production of these products is often subject to large batch variations, is time-consuming, and must be performed by well-trained personnel. To meet clinical requirements, it is therefore essential to develop reproducible and robust manufacturing processes.
Work in biological laboratories is characterized by frequently repeated, protocol-bound processes. In addition, there are often strict process conditions such as sterility and small tolerance windows for process parameters. In order to increase productivity and reproducibility while reducing costs in view of the resulting susceptibility to faults and the high intensity of work, the Fraunhofer IPT is researching automation solutions for laboratory processes. The integration of smart devices enables user-friendly process monitoring.
Automated stem cell production in the bioreactor for regenerative medicine
The Fraunhofer IPT is participating in the project based on its experience and expertise in the development of fully automated manufacturing facilities for stem cells, which was gained in the "StemCellFactory" project, among others.
Here, the manual production process of MSCs developed in the project will be analyzed and adapted so that it can be carried out completely by machine. The manufacturing facility is then conceptualized, the individual modules designed, the automation technology laid out and the control software developed.
The result is a facility for bioreactor-based, highly scaled production of mesenchymal stem cells (MSCs). The cells are propagated automatically in a bioreactor, supplied with new culture medium and counted regularly to determine their growth rate. Once the target number of cells is reached, they are automatically removed from the bioreactor, separated from their nutrient medium, and pipetted into special cooling vessels in special medium to be stored at -80°C. Although this process was designed for and tested with MSCs, it can also be transferred to other cell types.
Since all work steps require no human intervention, the risks of errors and contamination are particularly low. The modular system has facilities for real-time process control as well as cell quality monitoring, which are coordinated via the plant software. The production platform delivers MSC liquid cultures on a liter scale and, with its integrated close-meshed quality control, has decisive prerequisites for clinical application. The knowledge gained in the "AUTOSTEM" research project thus points the way to the development of strategies for the cost-efficient production of therapeutic cell cultures and brings innovative stem cell-based therapeutic approaches closer to widespread implementation.
- National University of Ireland Galway (REMEDI), Ireland
- Cell and Gene Therapy Catapult (CAT), United Kingdom
- Crospon (CP), Ireland
- Fraunhofer Institute for Production Technology IPT, Germany
- GE Healthcare (GE), United Kingdom
- Loughborough University (LU), United Kingdom
- Orbsen Therapeutics (ORB), Ireland
- Pintail (PT), Ireland
- Tyndall Institute (TI), Ireland
- University of Genova (UG), Italy
More detailed information about the project and the developed technologies as well as news can be found on the project website: AUTOSTEM – stem cell manufacture (autostem2020.eu)