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Orthotopic Implantation of Patient-Derived Cancer Cells in Mice Recapitulates Advanced Colorectal Cancer
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Recapitulating Patient-to-Patient Colorectal Cancer Tumor Heterogeneity Using Patient-Derived Xenograft Cells in an

Iman Hassani1,2, Benjamin Anbiah1, Yuan Tian1

  • 1Department of Chemical Engineering, Auburn University, Auburn, AL 36849, USA.

Biorxiv : the Preprint Server for Biology
|December 25, 2025
PubMed
Summary

3D engineered colorectal cancer tissues (3D-eCRC-PDX) successfully mimic patient tumor microenvironment heterogeneity. These models maintain patient-specific characteristics, offering a valuable tool for colorectal cancer (CRC) research.

Keywords:
PDXcancer tissue engineeringcolon cancerorganoidstiffnesstumor microenvironment

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Area of Science:

  • Oncology
  • Biomaterials Science
  • Cancer Biology

Background:

  • Colorectal cancer (CRC) progression is influenced by tumor microenvironmental heterogeneity, including stromal cells and mechanical properties.
  • Developing in vitro models that recapitulate this heterogeneity is crucial for advancing CRC research.

Purpose of the Study:

  • To evaluate the ability of 3D engineered CRC-PDX (3D-eCRC-PDX) tissues to recapitulate patient-specific heterogeneity.
  • To assess the maintenance of cellular subpopulations and mechanical properties in 3D-eCRC-PDX tissues over time.

Main Methods:

  • CRC-PDX tumor cells from three patients (stages II, III-B, IV) were encapsulated in PEG-fibrinogen hydrogels to create 3D-eCRC-PDX tissues.
  • Tissues were cultured in vitro for 29 days.
  • Transcriptomic analysis and principal component analysis were performed.

Main Results:

  • 3D-eCRC-PDX tissues mimicked patient-specific growth rates and mechanical stiffness of originating tumors.
  • Key cellular subpopulations, including cancer cells, stromal cells, and proliferative cells (CK20+), were maintained, unlike in 2D cultures.
  • Transcriptomic data clustered 3D-eCRC-PDX tissues and PDX tumors by patient, indicating similar gene expression profiles.

Conclusions:

  • 3D-eCRC-PDX tissues effectively recapitulate patient-specific tumor microenvironment heterogeneity in vitro.
  • These engineered tissues represent a promising tool for colorectal cancer research, preserving crucial patient-specific characteristics.