This Is AuburnElectronic Theses and Dissertations

Engineered Colorectal Cancer Tissues Employing Patient-derived Cells for Recapitulating the Tumor Microenvironment




Hassani, Iman

Type of Degree

PhD Dissertation


Chemical Engineering

Restriction Status


Restriction Type


Date Available



Colorectal cancer (CRC) remains the third most prevalent cancer and the third-highest cause of cancer-related deaths among both men and women in the United States. The development of pre-clinical CRC models is vital for understanding tumor biology to identify new, effective anti-cancer therapeutics. However, the current CRC models are unable to accurately represent disease pathophysiology and the complex tumor microenvironment. Patient-derived xenografts (PDXs), an in vivo model, demonstrate high potential in clinical translatability due to the recapitulation of key characteristics of the patient tumor; however, the use of PDXs is costly and low-throughput. This research focuses on the establishment of an in vitro 3D engineered CRC model using cells isolated from CRC PDX (CRC-PDX) tumor lines to recapitulate the key attributes of the originating tumors. This study demonstrates the use of poly(ethylene glycol)-fibrinogen (PEG-Fb) hydrogels for CRC tissue engineering. Chapter 1 introduces the current preclinical CRC models and the need for better models to recapitulate the CRC tumor microenvironment. Chapter 2, as a proof of concept, demonstrates the ability of a PEG-Fb-based tissue-engineered cancer model to support the investigation of CRC cell line phenotypes. Chapter 3 describes the establishment of engineered CRC tissue that recapitulates the key attributes of a stage II CRC-PDX tumor line. In Chapter 4, two other PDX lines originated from stages III-B and IV of CRC patients were incorporated into the tissue-engineered CRC model to recapitulate patient-to-patient and/or cancer stage-to-stage variabilities. Chapter 5 describes the rapid generation of CRC tissue-engineered microspheres for high-throughput study. Overall, the robust in vitro tissue-engineered CRC models reported in this research demonstrate significant potential for future implementation in the study of disease progression, tumorigenic mechanisms, and drug-testing applications.