In the context of personalized medicine, individualized pharmacotherapy is becoming increasingly important. In this context, agent identification, agent dosage and the prediction of undesirable side effects are the central parameters. Until now, such predictive studies have been based predominantly on genetic studies or clinical findings. Recent advances in the field of cell reprogramming open up the possibility to perform agent studies directly on human cells affected by the respective disease, which can be obtained directly from the patient.
In the StemCellFactory III project, now in its third funding phase, this unique resource is being exploited to develop cellular assay systems for agent testing and personalized pharmacotherapy in the field of neuropsychiatric disorders. Based on a structure for automated cell reprogramming of skin fibroblasts (StemCellFactory), which has already been developed by the project partners and is unique in Europe, procedures for the automated production of patient- and disease-specific induced pluripotent stem cells (iPS cells) from easily obtained blood samples are being developed in the now third project phase. In order to optimally map the effect of individual genetic changes on cellular disease processes, the genome editing method (CRISPR-Cas9), which has only recently become available, is being integrated as an automated process for the first time. Brain tissue-like 3D aggregates (organoids) generated from the iPS cells in a standardized manner will be used for metabolic studies for patient-specific agent dosage as well as prediction of effect and side effects. For this purpose, test systems and platform technologies will be generated for direct application in therapy planning and development, the exploitation of which will be carried out by companies participating in the consortium as well as already established links to external partners from the pharmaceutical industry.
Role of the Fraunhofer IPT
In addition to coordinating the research project "StemCellFactory III", the Fraunhofer IPT is responsible in particular for risk, data and quality assurance management in accordance with GMP guidelines as well as for upgrading the hardware and software of the StemCellFactory.
On the one hand, a concept for quality assurance management is to be developed that will allow the StemCellFactory to be used as a production platform for pharmaceutically relevant cell products. For this purpose, the StemCellFactory will be examined with regard to its conformity with good manufacturing practice (GMP) and the associated regulatory requirements. In a guided process, all existing protocols, the materials used, the integrated devices and software as well as other directly influencing factors are analyzed with regard to their compliance with GMP guidelines. Based on the results of the analysis, concrete technical and organizational solutions are developed for all critical points in the platform or process and recorded in a catalog of measures. At the same time, all newly developed processes are checked for GMP conformity prior to integration on the SCF.
For increased rough and detailed planning of processes and resources as well as for central data management, the StemCellFactory will also be expanded to include an MES. This ensures resource management, order monitoring and access rights management. This guarantees above all the protection of sensitive patient data as well as the IT security of the StemCellFactory.
- Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)
- Fraunhofer Institute for Productiontechnology IPT
- Lead Discovery Center (LDC)
- P3 aviation GmbH
- Uniklinik Aachen (UKA)
- Universitätsklinikum Bonn (UKB)
More detailed information about the project and the developed technologies, as well as news can be found on the project homepage www.stemcellfactory.eu/en.