Rapid tissue prototyping with micro-organospheres.

Abstract

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.stemcr.2022.07.016

Publication Info

Wang, Zhaohui, Matteo Boretto, Rosemary Millen, Naveen Natesh, Elena S Reckzeh, Carolyn Hsu, Marcos Negrete, Haipei Yao, et al. (2022). Rapid tissue prototyping with micro-organospheres. Stem cell reports, 17(9). pp. 1959–1975. 10.1016/j.stemcr.2022.07.016 Retrieved from https://hdl.handle.net/10161/26393.

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Scholars@Duke

Heaton

Brook Heaton

Assistant Research Professor of Molecular Genetics and Microbiology
Jang

David W Jang

Associate Professor of Head and Neck Surgery & Communication Sciences

My clinical expertise is in diseases of the nose, sinuses, and skull base.  I perform endoscopic sinus surgery, nasal airway surgery, and minimally invasive endonasal surgery of the pituitary and skull base. 

Glass

Carolyn Glass

Associate Professor of Pathology

Cardiothoracic Pathologist and Physician-Scientist
Division Chief, Cardiovascular Pathology 
Co-Director, Division of Artificial Intelligence and Computational Pathology
Associate Director, Residency Program  
Director, Duke University Hospital Autopsy Service 

Dr. Glass completed medical residency in Anatomic Pathology at the Brigham and Women’s Hospital/Harvard Medical School followed by fellowships in Cardiothoracic Pathology also at Brigham and Women’s Hospital/Harvard Medical School and Pulmonary/Cardiac Transplant Pathology at the University of Texas Southwestern Medical Center. Dr. Glass initially trained as a vascular surgeon with a focus on endovascular/interventional procedures through the 0+5 Integrated Vascular Surgery Program at the University of Rochester Medical Center from 2007-2011.  As a recipient of the NIH National Lung Blood Institute T32 Ruth Kirschstein National Service Research Award, she completed a Ph.D with a concentration in Genomics and Epigenetics in 2014. Dr. Glass serves as P.I. of multiple NIH grants, including U54 and SBIR.

As a thoracic surgical pathologist, Dr. Glass diagnoses complex heart transplant rejection and thoracic malignancies. She works closely with the Duke Thoracic Oncology Group, DCI Center for Cancer Immunotherapy, Duke Division of Cardiovascular Medicine and Cardiothoracic Surgery and Pratt School of Biomedical Engineering. 

Dr. Glass is the recipient of the Society of Cardiovascular Pathology (SCVP) Young Investigator’s Award, the William von Liebig Vascular Biology Research Fellowship at the Harvard Institutes of Medicine, the Duke Pathology Salvatore V. Pizzo Faculty Research Mentor Award, the Duke Department of Pathology Early Career Research Achievement Award and is author of over 85 publications (including book chapters in the recent W.H.O. Classification Tumours of the Lung, Pleura, Thymus and Heart) and 50 national presentations in cardiovascular disease, thoracic malignancies, surgery and machine learning. 

In addition to her clinical and research activities, Dr. Glass serves on the Executive/National Committees for the Society of Cardiovascular Pathology, College of American Pathology Artificial Intelligence Committee and the Duke School of Medicine Executive Admissions Committee. 




Heaton

Nicholas Scott Heaton

Associate Professor of Molecular Genetics and Microbiology

Our research group is primarily interested in the study of respiratory RNA viruses.  We have published work on viruses of the families: orthomyxoviridae, paramyxoviridae, and coronaviridae.  The research in our laboratory is predominantly focused understanding the mechanisms of viral pathogenesis with the ultimate goal of developing new therapies that can be used to combat both current and future viral diseases.

Shen

Xiling Shen

Adjunct Professor in the Department of Pathology

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).


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