Stem Cells and Organoid Technology in Precision Medicine in Inflammation: Are We There Yet?
Tran F., Klein C., Arlt A., Imm S., Knappe E., Simmons A., Rosenstiel P., Seibler P.
Individualised cellular models of disease are a key tool for precision medicine to recapitulate chronic inflammatory processes. Organoid models can be derived from induced pluripotent stem cells (iPSCs) or from primary stem cells ex vivo. These models have been emerging over the past decade and have been used to reconstruct the respective organ-specific physiology and pathology, at an unsurpassed depth. In cancer research, patient-derived cancer organoids opened new perspectives in predicting therapy response and provided novel insights into tumour biology. In precision medicine of chronic inflammatory disorders, stem-cell based organoid models are currently being evaluated in pre-clinical pharmacodynamic studies (clinical studies in a dish) and are employed in clinical studies, e.g., by re-transplanting autologous epithelial organoids to re-establish intestinal barrier integrity. A particularly exciting feature of iPSC systems is their ability to provide insights into organ systems and inflammatory disease processes, which cannot be monitored with clinical biopsies, such as immune reactions in neurodegenerative disorders. Refinement of differentiation protocols, and next-generation co-culturing methods, aimed at generating self-organised, complex tissues in vitro, will be the next logical steps. In this mini-review, we critically discuss the current state-of-the-art stem cell and organoid technologies, as well as their future impact, potential and promises in combating immune-mediated chronic diseases.