Rapid tissue prototyping with micro-organospheres.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Wang Zhaohui, Boretto Matteo, Millen Rosemary, Natesh Naveen, Reckzeh Elena S, Hsu Carolyn, Negrete Marcos, Yao Haipei, Quayle William, Heaton Brook E, Harding Alfred T, Bose Shree, Driehuis Else, Beumer Joep, Rivera Grecia O, van Ineveld Ravian L, Gex Donald, DeVilla Jessica, Wang Daisong, Puschhof Jens, Geurts Maarten H, Yeung Athena, Hamele Cait, Smith Amber, Bankaitis Eric, Xiang Kun, Ding Shengli, Nelson Daniel, Delubac Daniel, Rios Anne, Abi-Hachem Ralph, Jang David, Goldstein Bradley J, Glass Carolyn, Heaton Nicholas S, Hsu David, Clevers Hans, Shen Xiling
Аннотация
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.