Speaker
Description
3D biological models able to reproduce the physiology and the behavior of human tissues/organs are the focus of the newest groundbreaking research, enabling the scientific advancement of personalized medicine while simultaneously adhering to the principle of the 3Rs. Among the key features necessary to achieve a physiological and functional 3D model, there is the ability to replicate an immune response after stimuli. During the immune response, the immune system recognizes substances or microorganisms, for the purpose of defending against exogenous factors. The immune response, as the inflammation, implies the ability to recruit immune cells, as lymphocytes, granulocytes, monocytes, macrophages and others, in the damaged site of the skin, activating biological cascades of signals which matures the inflammatory response. Reproduce the complete and complex response to pathogens of in vitro immune system, considering both resident and circulating, is almost unexplored in literature for 3D skin model.
In this contest, a particular focus can be put on the behavior of monocytes and macrophages, which play a crucial role in the pro- and anti-inflammation processes, within the biological 3D skin model previously developed in our lab. This 3D model is composed by the epidermis and dermis layers, which are constitute respectively by human keratinocytes and human fibroblasts. Fibroblast are embedded in gelatin methacryloyl (GelMA) to obtain a three-dimensional structure with cell-embedded. The ability to act as a barrier was verified.
The research here presented directs its attention to the differentiation and polarization processes of monocytes and macrophages. They were cultured within the gelatin methacryoyl matrix in different radio and concentration. The differentiation process, as well as signaling processes between cells of the same type and between monocytes and macrophages, were extensively analyzed by fluorescence microscopy, digital PCR, colorimetric analysis.
Further analysis were conducted to unveil details on the interaction between macrophages, monocytes and other immune cells, as healthy lymphocytes, when embedded in gelatin methacryloyl.
The incorporation of immune cells, into the existing epidermis-dermis skin model creates a more advanced and physiologically relevant platform for drug and therapy screening. This innovation will greatly improve the model’s functionality, providing a dynamic system for studying skin-related immune reactions. By closely mimicking the interactions between skin tissues and the immune system, this model will serve as a valuable tool for investigating disease mechanisms and therapeutic responses.
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