Rapid tissue prototyping with micro-organospheres.
In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.
Duke Scholars
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- Precision Medicine
- Organoids
- Microfluidics
- Humans
- Drug Evaluation, Preclinical
- Antineoplastic Agents
- 3101 Biochemistry and cell biology
- 1103 Clinical Sciences
- 0601 Biochemistry and Cell Biology
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Precision Medicine
- Organoids
- Microfluidics
- Humans
- Drug Evaluation, Preclinical
- Antineoplastic Agents
- 3101 Biochemistry and cell biology
- 1103 Clinical Sciences
- 0601 Biochemistry and Cell Biology