“Organ on Chip Platforms for Modeling Human Disease”
Host: Lori Setton (WashU Biomedical Engineering)
Abstract We report the design and fabrication of robust fluidic platforms that are optimal for culturing and interrogating 3D organoid cultures. The optimized design of convective fluid flows, use of bio-inert and non-absorbent materials, reversible assembly of the platform, manual access for loading and unloading of cultures, and straightforward integration with commercial imaging and fluid handling systems are major improvements over conventional PDMS-based low volume microfluidics. The platform has been used for perfusion interrogation of human pancreatic islets, and engineered spheroid cultures that mimic the metastatic niche of the bone marrow. Human pancreatic islets were tested for dynamic secretion of hormones, concomitant live-cell imaging, and optogenetic stimulation of genetically engineered islets. The efforts to evaluate ex vivo function of islets are informing the clinical trials currently underway to transplant human islets in Type 1 Diabetic patients. The platform is also being tested for long term culture of spheroids composed of primary human cells of the bone marrow along with vascular cells and supporting pericytes. The efforts to recreate the metastatic niche are enabling in vitro maintenance and propagation of circulating tumor cells derived from the blood of breast and prostate cancer patients, as tools for enabling precision oncology.
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