New Basement Membrane Extract Discovery Lifts Uncertainty For Clinical Trials

By Irene Yeh

March 21, 2024 | Patient-derived organoids (PDOs) are 3D cell cultures that mimic organs or tissues. Extracted from a patient’s cell or tissue samples, these cultures can be tested with different drugs, thus providing a more personalized approach to treatment options. Because PDOs have greatly helped with finding the right treatment for patients, they have become increasingly more accessible for researchers and clinical studies.  

To cultivate organoids, a basement membrane extract (BME) is required. BMEs are usually commercially available, but with the ongoing supply chain issues caused by the COVID-19 pandemic, some clinical sites may not have access to the BME they use. Some may even be severely limited or restricted.  

But do different BME brands affect drug responses and gene expressions in organoids? It is important to address this concern because it can offer the assurance that researchers do not need to spend time tracking down the BMEs their clinical site commonly uses and can expand to other more accessible brands. To determine the answer, researchers at the Salk Institute tested out different BMEs to see their effects on pancreatic cancer organoids. 

The Salk Institute’s Experiment 

The research team at the Salk Institute experimented with different BMEs to determine their effects on proliferation, drug response, and gene expression in human and mouse PDOs. The BMEs used were Matrigel, Cultrex, and UltiMatrix.  

The study found that these commercial BMEs had no significant changes to the PDOs’ gene expressions or drug responses, including PDOs’ sensitivity to chemotherapies and targeted therapies. Six different pancreatic cancer drugs—Gemcitabine, Abraxane, Oxaliplatin, Irinotecan, Fluorouracil, and Trametinib—were tested on these organoids. None of them exhibited “consistent or substantial shifts when cultured in different BMEs” (JCI Insight, DOI: 10.1172/jci.insight.172419). However, it was found that Matrgiel had a 75% generation efficiency of pancreatic cancer organoids, which is faster than Cultrex and UltiMatrix.  

While the study confirmed that BME brand does not affect pancreatic cancer organoids’ drug response and gene expressions, it is still unknown if BME affects different organoids. But the results of the Salk Institute’s study can provide assurance for researchers that the brand of BME used will not have an impact on their PDOs. With the supply chain issues continuing to negatively affect the industry, clinical sites can use the BME that is most accessible and available to them.  

Quicker Organoid Growth Means Quicker Testing 

Faster organoid growth is beneficial for researchers because it allows them to conduct treatment experiments sooner—and patients can receive and change treatment sooner, too. This is especially critical information for pancreatic cancer research. With a 12% survival rate over a 5-year period, pancreatic cancer is one of the most aggressive cancers due to the tumor cells’ rapid growth rate (JCI Insight, DOI: 10.1172/jci.insight.172419). This makes them particularly prone to drug resistance. With quicker PDO growth, researchers can begin testing earlier and provide patients with treatment sooner.