For cell-based therapies (CBT), primary (stem) cells are isolated from the patient, expanded in vitro and then used (1) for cell therapy (stem cells therapy, gene therapy), (2) for the production of cellular products (e.g. extracellular vesicles, growth factors), (3) tissue engineering products (e.g. skin, bone, cartilage), and (4) in vitro test systems (cell-based assays, disease models).
However, the capacity of primary stem cells to maintain their in vivo functionalities during in vitro cultivation is compromised by standard culture conditions because they do not recapitulate the in vivo situation. In contrast, it is crucial to mimic the physiologic situation to maintain cellular functionalities for successful applications in CBT. To gain results from cell-based assays that resemble the in vivo condition and therefore can be considered as relevant for translation onto the human organism, not only the cellular environment has to mimic the in vivo situation but also the cells have to be isolated, expanded, differentiated and cultured under conditions that do not alter their original behavior nor characteristics due to an artificial environment or treatment. A physiologic cell culture environment can be achieved by establishing 3D cultivation, physiologic (hypoxic) oxygen concentrations, dynamic culture conditions and by using cell culture media which closely resemble the in vivo fluids.
Therefore, we strive for optimizing 3D conditions already from isolation and expansion to facilitate the generation of „healthy“ cells and effective cell based productsTo guide cellular differentiation processes we utilize functional 3D tissue-like structures under defined and controlled dynamic conditions, using specialized incubator and bioreactor systems and feeding strategies to enable a more physiological cellular development.
For a safe translation to clinical application all CBT products should be produced in a physiological setting, including dynamic 3D culture conditions, hypoxic O2 concentration, and xeno-free culture media.