Patient-derived mini-colons enable long-term modeling of tumor–microenvironment complexity

Rheumatology and Immunology Gastroenterology Medicine Cell Biology Bioengineering Oncology Life Sciences
organ-on-chip patient colorectal cancer colon mucosa CAF TIL CRC

Long-term Model for Studying Tumor Microenvironment Complexity: Patient-derived Mini-colons

Background:

Patient-derived Mini-colons The interaction between tumors and their surrounding microenvironment has profound implications for cancer development and treatment. However, existing in vitro tumor models lack the ability to capture these complex interactions. To address this issue, this study innovatively developed a mini-colon model based on patient-specific cancer cells and their microenvironment, providing a new experimental platform for cancer treatment.

Research Team and Publication Information:

This study was led by L. Francisco Lorenzo-Martin and others from the Laboratory of Stem Cell Bioengineering at the Swiss Federal Institute of Technology Lausanne (EPFL), along with several other research institutions. The research results were published in Nature Biotechnology.

Research Process:

  1. Research Objectives and Design: To overcome the limitations of existing models, this study aimed to develop a system capable of long-term stable modeling of the complexity of tumors and their microenvironment. The research focused on colorectal cancer (CRC) and generated mini-colons containing healthy human colonic epithelium, stably integrating cancer cells and their native microenvironment.

  2. Model Establishment: Using tissue engineering and microfabrication techniques, the study reconstructed CRC and its tumor microenvironment (TME) in mini-colons. This model was achieved through hydrogel chambers on microfluidic devices, including cancer cells, cancer-associated fibroblasts (CAFs), tumor-infiltrating lymphocytes (TILs), and other microenvironment components.

  3. Key Findings: The mini-colons demonstrated potential in drug evaluation, investigation of cancer cell invasion mechanisms, and assessment of tumor immune responses and immunotherapy strategies. Notably, the study revealed the mechanism by which cancer-associated fibroblasts promote cancer cell invasion by inducing the production of metalloproteinase MMP7. Additionally, the study showed that CAFs could promote immune evasion by increasing the expression of PD-L1 on cancer cell surfaces.

  4. Conclusion and Significance: The mini-colon model provides a new experimental platform for cancer research and treatment, with broad application prospects in precision medicine, drug screening, and cancer biology research. The development of this model offers an important tool for studying the complex tumor microenvironment, enhancing our understanding of tumor growth, metastasis, and interactions with the immune system, and laying a solid foundation for developing new cancer treatment strategies.

Research Highlights:

  • Successfully constructed a mini-colon model integrating a real tumor microenvironment;
  • Revealed the mechanism by which CAFs promote CRC invasion through MMP7;
  • Validated the potential application of the mini-colon model in evaluating anti-cancer drug effects, elucidating tumor invasion mechanisms, and assessing immunotherapy strategies.

This study not only provides powerful new tools for cancer research but also opens new doors for future cancer treatment innovations.