Rapid tissue prototyping with micro-organospheres

Zhaohui Wang, Matteo Boretto, Rosemary Millen, Naveen Natesh, Elena S Reckzeh, Carolyn Hsu, Marcos Negrete, Haipei Yao, William Quayle, Brook E Heaton, Alfred T Harding, Shree Bose, Else Driehuis, Joep Beumer, Grecia O Rivera, Ravian L van Ineveld, Donald Gex, Jessica DeVilla, Daisong Wang, Jens Puschhof, Maarten H Geurts, Athena Yeung, Cait Hamele, Amber Smith, Eric Bankaitis, Kun Xiang, Shengli Ding, Daniel Nelson, Daniel Delubac, Anne Rios, Ralph Abi-Hachem, David Jang, Bradley J Goldstein, Carolyn Glass, Nicholas S Heaton, David Hsu, Hans Clevers, Xiling Shen

Published: 13 September 2022


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.

Full Access Link: Stem cell reports