Postdoctoral Fellow University of Victoria Oak Bay, British Columbia, Canada
Introduction:: Alzheimer's disease (AD) and other forms of dementia affect approximately 25 million people worldwide, with that number expected to double in the next 20 years. The overexpression of cytokines and other pro-inflammatory molecules by microglia increases the formation of beta-amyloid aggregates in the cells, promoting the death of neural cells. Here, a brain-on-a-chip model is being developed to determine the effect of pro-inflammatory molecules produced by macrophages on the formation of beta-amyloid aggregates and cell death in neural cells derived from AD patients, as well as to test potential drugs that could potentially reduce the secretion of these molecules.
Materials and Methods:: This customized lab-on-a-chip model consists of two chambers, one for the human induced pluripotent stem cells (hiPSC)-derived AD-neural progenitor cells (NPCs) and the other for monocytes derived macrophages, separated by a semi-permeable membrane. The membrane allowed the exchange of cell signals while limiting cell migration to allow assessment of paracrine communication between cells. Cellink's BIOX bioprinter was used to create six-layer cylindrical constructs from the hiPSC-derived AD-NPCs, which were then transferred to customized silicone chips. These constructs were then cultured, and their characteristics were studied for 21 days. Cell viability assessment has done by live and dead and Alamar Blue assay on day 1, 14, and 21.
Results, Conclusions, and Discussions:: The generated tissues demonstrated after culturing one day on-a-chip cells were viable and evenly distributed with very few dead cells. Alamar Blue results on day one suggest good cellular metabolic activity. These bioprinted brain-on-a-chip models might be studied to better understand the disease's pathogenesis. This neuro-immune model-on-a-chip have the potential to mimic the architectures of intricate tissue for use in AD physio-pathological studies.
