Microphysiological Systems Improve Colorectal Cancer Research

By Caroline Zielinski

Biomarkers in Colorectal Cancer Patients

Colorectal Cancer (CRC) affects the lower end of the digestive tract. Almost 150,000 American adults are diagnosed with CRC yearly, and it is the second leading cause of cancer-related deaths1. This type of cancer develops from abnormal cell replication, leading to a clump of cancerous cells in the mucosa of the colon or rectum.
 

Figure 1: The human digestive tract which includes the small intestine (the pink, purple and yellow areas), the stomach (the red area) and the large intestine, or colon, which is the faded red area surrounding the the small intestine. 

These cell clumps (aberrant cysts) transform into more severe tumors over 10-20 years, becoming adenomas and then adenocarcinomas2. Adenomas are cells that are not yet malignant but might develop into malignant and possibly metastatic tumors. They have marked boundaries and display varying degrees of dysplasia. The three different levels of dysplasia are called tubular, villous, and tubulo-villous. The level of dysplasia can be an informative biomarker of the increased cancer risk3. These markers, and other markers that show the possibility of colorectal cancer forming, can then be used to test different treatments4.

3D Organoid Models for Studying Colorectal Cancer

To date, colorectal cancer studies mostly involve animal models. Although animal models have provided useful information on how colorectal cancer develops, using them raises ethical concerns, and they may not represent the disease progression and treatment responses in humans. Three-dimensional organoid models provide a promising alternative as they would better recapitulate disease conditions and cancer environments in humans. The more realistic cancer environments provided by organoids allows extensive research into possible treatment and preventive measures4. Furthermore, patient-derived organoids open doors to improve personalized treatment options for colorectal cancer patients.

Synthetic Biology: Co-Culturing Technologies

A limitation of organoid use is that other supporting cell types might not be examined simultaneously, resulting in an incomplete representation of the human organ. Co-culturing approaches attempts to solve this issue by incorporating multiple cell types to evaluate the interactions between tumor cells and surrounding cells2. Co-culturing thus allows more accurate investigations into possible colon cancer treatments. Emerging 3D in vitro platforms such as Lena Biosciences' PerfusionPal is an innovative platform for the co-culture of several cell types to model colorectal tumors [Figure 2]. One of the key differentiators for the PerfusionPal system is the use of a blood substitute to improve oxygenation of cultured cells to increases viability for long term studies. Tumors cultured in the PerfusionPal system represent the native tumors and can be used to study tumor biology and evaluate the efficacy of anticancer therapeutics.
 

Figure 2: PerfusionPal from Lena Biosciences is an innovative platform for the co-culture of several cell types to model colorectal tumors. (A) The insert system and (B) The 3 components of the 48-well system including the lid, multi-well insert and tray, along with the SeedEZ scaffold, culture medium and blood substitute
 


 

Resources 

  1. Colorectal Cancer - Statistics. (2020, March 10). Cancer.Net. https://www.cancer.net/cancer-types/colorectal-cancer/statistics
  2. Goers, L., Freemont, P., & Polizzi, K. M. (2014). Co-culture systems and technologies: taking synthetic biology to the next level. Journal of the Royal Society, Interface11(96), 20140065. https://doi.org/10.1098/rsif.2014.0065
  3. Steinwachs D, Allen JD, Barlow WE, et al. NIH state-of-the-science conference statement: Enhancing use and quality of colorectal cancer screening. NIH Consensus and State-of-the-science Statements. 2010 Feb;27(1):1-31.
  4. Fang, Y., & Eglen, R. M. (2017). Three-Dimensional Cell Cultures in Drug Discovery and Development. SLAS discovery: advancing life sciences R & D22(5), 456–472. https://doi.org/10.1177/1087057117696795