Dr. Huayu Yang is a professor in the Department of Liver Surgery at Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences. She graduated from the Peking University Health Science Center (PUHSC) in 2002 and obtained her PhD degree in pharmacology from PUHSC in 2007. In 2011, she completed postdoctoral training in PUMCH under the supervision of Prof. Jiefu Huang. After that, she worked as an assistant professor and associate professor in the Department of Liver Surgery, PUMCH. The recent research focuses on the application of 3D bioprinting technology in liver disease, tumor and drug research. She is the PIs of several research projects and has published more than 100 articles in domestic and international journals. Among them, 3 articles were selected as ESI Highly Cited Articles, and representative works were published in top journals, such as GUT, Nature Communications, Biomaterials, Advanced Science, and so on. She was awarded the Third Prize of Chinese Medical Science and Technology Award and served as an editorial board member of Hepatobiliary Surgery and Nutrition (SCI IF: 8.0).

Topic title: Multicellular 3D Bioprinted Human Gallbladder Carcinoma for in vitro Mimicry of Tumor Microenvironment and Intratumoral Heterogeneity

Abstract:

Gallbladder carcinoma (GBC) is a malignant hepatobiliary cancer characterized by intricate tumor microenvironments (TME) and heterogeneity. The existing GBC in vitro models could not faithfully restore its characteristics. Three-dimensional (3D) bioprinting enables establishment of multicellular GBC models with high-throughput and high fidelity. In this study, we designed a concentric cylindrical tetra-culture model to reconstitute the spatial distribution of cells in tumor tissue, with inner part containing GBC cells, and the outer ring a mixture of endothelial cells, fibroblasts, and macrophages. We confirmed the survival, proliferation, biomarkers and gene expression profiles in GBC 3D tetra-culture models. H&E and immunofluorescence staining verified the morphologies and robust expression of GBC/endothelial/fibroblast/macrophage biomarkers in GBC 3D tetra-culture models. Single-cell RNA sequencing revealed two distinct subtypes of GBC cells within the model including glandular epithelial and squamous epithelial cells, suggesting the mimicry of intratumoral heterogeneity. Comparative transcriptome profile analysis among various in vitro models revealed that cellular interactions and TME in 3D tetra-culture models reshaped the biological processes of tumor cells to a more aggressive phenotype. GBC 3D tetra-culture models restored the characteristics of TME as well as intratumoral heterogeneity. Therefore, this model is expected to have future application in the research of tumor biology and anti-tumor drug development.