Miniature ‘organs in a dish’ used to identify drugs that fight COVID-19

Organoids – the mini organs grown in lab dishes by using human pluripotent stem cells (hPSCs) capable of becoming any type of tissue – have for the first time been used to quickly identify several drugs capable of preventing infection with SARS-CoV-2, the virus that causes COVID-19.

“It’s critical that we develop these sorts of scientific models to allow us to more accurately study the behavior of SARS-CoV-2 in human cells,” said Huanhuan Joyce Chen, PhD, an assistant professor in the Pritzker School of Molecular Engineering and Ben May Department for Cancer Research at the University of Chicago. “The use of human cell-based models derived from hPSCs can help significantly improve the screening and study of effective COVID-19 drug treatments.”

The study is published in the journal Nature.

Currently, scientists rely on different types of models for development of treatments for COVID-19. Each approach has its limits as a model meant to naturally replicate the structure and function of human cells. For instance, with animal models, lab mice may be commonly used for research, but regular mice are not affected by SARS-CoV-2 and must instead be genetically altered to make them susceptible to the virus. Other research animals can be infected by SARS-CoV-2, but exhibit different COVID-19 symptoms from those of infected humans.

Using organoids derived from human pluripotent stem cells allows scientists to study how actual human cells in an organ-like setting are affected by SARS-CoV-2.

Chen, whose lab specializes in tissue engineering and stem cell biology, provided the hPSC-derived cell models used in the research.

For the study, the scientists grew two types of tissue: lung tissue because SARS-CoV-2 primarily infects the respiratory tract, and colon tissue because 25 percent of COVID-19 patients also experience gastrointestinal symptoms like diarrhea and vomiting. These patients are prone to experiencing worse outcomes from the disease.

The team screened a library of FDA-approved medications in organoids and validated the drugs in xenograft lung tissues by implanting the hPSC-lung cells in immunocompromised mice. Three of the compounds prevented the virus from infecting the lung and colon cells: the chemotherapy drug imatinib, the antimalarial drug quinacrine dihydrochloride, and mycophenolic acid, an immunosuppressant used to prevent organ rejection after transplantation.

Several clinical trials are examining the effectiveness of imatinib in treating COVID-19 patients.

“The usefulness of these drugs in human clinical trials remains to be determined, but we’re excited to develop an experimental approach to studying COVID-19 in human cells,” said Chen.

“Identification of SARS-CoV-2 Inhibitors Using Lung and Colonic Organoids” was written by Huanhuan Joyce Chen and Fuyu Duan of the University of Chicago, Yuling Han, Xiaohua Duan, Liuliu Yang, Xuming Tang, Jianjun Zhu, Zeping Zhao, Fong Cheng Pan, Todd Evans, Shuibing Chen, Tomer M. Yaron, Jared L. Johnson, Lewis C. Cantley, Tuo Zhang, Dong Xu, Xing Wang, Jenny Xiang, Yaron Bram, Duc-Huy T. Nguyen, Robert E. Schwartz, Chanel Richardson, David Redmond, Sean Houghton, Jose Jessurun and Alain Borczuk of Weill Cornell Medicine, Benjamin E. Nilsson-Payant, Skyler Uhl and Benjamin R. tenOever of Icahn School of Medicine at Mount Sinai, Pengfei Wang, Yaoxing Huang and David D. Ho of Columbia University, Yuru Liu of the University of Illinois and Hui Wang of Shanghai Jiao Tong University.

The study was supported by Weill Cornell Medicine, the American Diabetes Association, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, the Defense Advanced Research Projects Agency, the Marc Haas Foundation and the Jack Ma Foundation.