RECODE: Real-time analysis and environmental feedback for directed differentiation of liver organoids

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Human stem cells can be grown into organ mimics, termed “organoids”. If they can faithfully reproduce the key structures and activities of organs, they would be extremely valuable. They could revolutionize the way we discover and test new drugs, study human disease, and possibly even replace damaged body parts. The technology to produce consistent and reliable organoids does not exist. This project will combine a novel type of live imaging microscopy with adaptive biomaterials technology to enable active monitoring and manipulation of liver organoids. As part of the project, the investigators will recruit and train diverse students at the high school, undergraduate, and graduate levels. They will also promote science activities to under-served elementary students, and engage in high school educator development.Three-dimensional (3D) culture of human stem cells as “organoids” has tremendous clinical potential. Applications include drug discovery, safety and efficacy testing, regenerative medicine, and as models of normal and diseased tissue development. An unmet requirement for the success of these applications is proper organoid differentiation and maturation. Through this RECODE project, a noninvasive imaging method to actively monitor human induced pluripotent stem cells (iPSCs) will be developed. This information will be used to manipulate adaptive biomaterials. These biomaterials will modulate matrix-mediated biomechanical and biochemical cues and reproducibly direct organoid differentiation. Finally, the improved reproducibility and functionality of the RECODE-differentiated organoids will be validated through assays that represent the three major potential applications for hepatic organoids: regenerative medicine, drug screening, and disease modeling. The novel technologies developed will have broad applicability to a variety of other cell, organoid, and tissue types.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.