Associate Professor Indiana University Bloomington Bloomington, Indiana, United States
Introduction:: The aging of the immune system drives systemic aging and the pathogenesis of age-related diseases. However, a significant knowledge gap remains in understanding immune-driven brain aging and Alzheimer’s disease (AD), due to the limited current in vitro models of neuro-immune interaction. Here we report the development of engineered human brain organoids to discover the dynamic process of immune-driven brain aging and AD progression.
Materials and Methods:: We engineer the organoids using 3D printing that can confine organoid growth and perfuse oxygen and nutrients (and immune cells) to generate standardized human cortical organoids that promote viability, and gene expression signatures that reflect organoid maturation as well as commit to forebrain identity. Dynamic rocking flow is incorporated into the platform that allows us to perfuse primary monocytes from AD and healthy donors (young and old) and culture human cortical organoids for modeling and analyzing the aged immune cell interacting with organoid tissues systematically.
Results, Conclusions, and Discussions:: We discovered that aged monocytes had increased infiltration and promoted the expression of aging-related markers within the human cortical organoids, indicating that aged monocytes may drive brain aging. We believe that the engineered human brain organoids provide promising solutions for basic research and translational applications in aging, neural immunological diseases, autoimmune disorders, and cancer.