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Harnessing Decellularized Extracellular Matrix for Enhanced Fidelity in Colorectal Cancer Organoid and Cell-Derived Xenograft Models

  • Yena Nam (Department of Physiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Eunju Cha (Department of Physiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • Su Min Kwak (Department of Medicine, College of Medicine, Yonsei University Graduate School) ;
  • Seung Ju Seo (Department of Physiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine) ;
  • John Hoon Rim (Department of Laboratory Medicine, Yonsei University College of Medicine) ;
  • Yoonhee Jin (Department of Physiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine)
  • Received : 2024.05.30
  • Accepted : 2024.06.14
  • Published : 2024.08.28

Abstract

This study evaluates the efficacy of a decellularized intestine tissue-derived extracellular matrix (Intestine ECM) as a scaffold for culturing colorectal cancer (CRC) organoids and establishing cell-derived xenograft (CDX) models, comparing its performance to traditional Matrigel. Intestine ECM demonstrates comparable support for organoid formation and cellular function, highlighting its potential as a more physiologically relevant and reproducible platform. Our findings suggest that Intestine ECM enhances the mimetic environment for colon epithelium, supporting comparable growth and improved differentiation compared to Matrigel. Moreover, when used as a delivery carrier, Intestine ECM significantly increases the growth rate of CDX models using patient-derived primary colorectal cancer cells. This enhancement demonstrates Intestine ECM's role not only as a scaffold but also as a vital component of the tumor microenvironment, facilitating more robust tumorigenesis. These findings advocate for the broader application of Intestine ECM in cancer model systems, potentially leading to more accurate preclinical evaluations and the development of targeted cancer therapies.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2021R1C1C2009131, No. 2022R1A2C1013380) and the Bio & Medical Technology Development Program of the NRF & funded by the Korean government (MSIT) (No. 2022M3A9B6082675). This work also supported by a grant (20024298) from the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).

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