4.8 Article

An Engineered Patient-Derived Tumor Organoid Model That Can Be Disassembled to Study Cellular Responses in a Graded 3D Microenvironment

期刊

ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 41, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202105349

关键词

3D model; hypoxia; patient-derived organoids; tumor microenvironment

资金

  1. Canadian Institute of Health Research
  2. Natural Sciences and Engineering Research Council of Canada (NSERC) via a Collaborative Health Research Program (CHRP) [146469]
  3. Janssen Inc.
  4. Ministry of Research and Innovation through the Ontario Centres of Excellence
  5. Canadian First Research Excellence Fund Medicine by Design Award
  6. Vanier Canada Graduate Scholarship
  7. NSERC M3 CREATE Fellowship
  8. NSERC CREATE TOeP scholarship
  9. CFREF Medicine By Design Fellowship
  10. Mary H. Beatty Fellowship
  11. Ontario Graduate Scholarship

向作者/读者索取更多资源

TRACER2 serves as a novel platform to dissect the effects of microenvironmental parameters on tumor cell function, especially in the study of pancreatic cancer PDOs.
Patient-derived organoids (PDOs) are emerging as powerful models to capture the genetic heterogeneity of human tumors. However, the self-assembling nature of PDOs limits their use in studies of the impact of microenvironmental heterogeneity on tumor cell function. Here, a paper-based model, the tissue roll for analysis of cellular environment and response (TRACER) using patterned polymer infiltration to enable controlled assembly and disassembly of organoid structures to study the impact of both genetic and microenvironmental heterogeneity on tumor cell behavior. In the adapted platform (TRACER2), pancreatic cancer PDOs establish oxygen gradients across the tissue and in response exhibit graded cell viability, proliferation, hypoxia-response gene transcription, and response to gemcitabine therapy. Further, PDOs retrieved from the hypoxic regions of the TRACER2 cultures show graded transcriptional changes in immunosuppression-related genes and upon co-culture, after TRACER2 disassembly, induce graded functional changes in Jurkat cells and macrophage cells. Therefore, TRACER2 offers a novel platform to dissect the effects of microenvironmental parameters on tumor cell function.

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