Immunosenescence and organoids: pathophysiology and therapeutic opportunities
Amirhossein Kamroo, Mahsa Hosseini Kakroudi, Amirreza Jabbaripour Sarmadian, Ayda Firouzabadi, Shaghayegh Mousavi, Niloufar Yazdanpanah, Kiarash Saleki, Nima Rezaei
Abstract
Immunosenescence is the gradual deterioration in the functionality of the immune system that has various clinical manifestations, such as a weakened response to vaccination, higher susceptibility to viral/bacterial/fungal infection, and higher incidence rates regarding the ageing-based disorders. Conventionally used models, like animal or 2D models for unraveling the interactions between ageing and immunity are unable to depict the complexity of bodily environments. However, this major limitation can be addressed via using the organoid technology. For clarification, organoids are tissue-resembling 3D structures that are generated from stem cells; they have the major superiority of preserving the human physiology, multicellular intricateness, and the capability of dynamic interactions between the existing elements. Organoid-based technology has been applied for the study of different organ-specific immunosenescence, such as in the intestine, brain, liver, and skin. Besides, organoids offer the bright innovative future of senolytic CAR T lymphocytes and other regenerative-based therapies. This review narrates the cutting-edge application of organoids and the mechanisms involved in the detailed molecular processes of organ-specific immunosenescence.