Did you know that getting a single drug approved can take around 20 years and cost millions of dollars? This lengthy process includes rigorous in vitro (lab-based), in vivo (animal testing), and clinical trials to ensure safety and efficacy.
But what if I told you that scientists are working on advanced 3D in vitro cell culture models that could bridge the gap between traditional 2D cell cultures and animal testing? These innovative models can potentially revolutionize drug development, saving both time and money.
3D in vitro cell culture models, like organoids and spheroids, are transforming research in fields like cancer biology. Unlike 2D cultures, which involve simple, flat layers of cells, 3D models better mimic the structural complexity of human tissues. This is particularly important in the study of metastatic prostate cancer, where the spatial organization of cells and the extracellular matrix (ECM) plays a crucial role. In 2D models, the simplicity of a single-cell layer fails to replicate the multi-layered, tumor-like architecture found in real tissues. The ECM, a network of proteins and molecules that provides structural support to cells, also influences how drugs penetrate and interact with cancer cells. In a 2D model, this matrix is often poorly represented, leading to inaccurate results. However, 3D models recreate the ECM distribution, offering a more realistic environment for testing drug responses and understanding cancer progression.
While in vivo studies using animal models add another layer of complexity to research, they come with their own challenges. Metastatic cancer cells are particularly difficult to study in animals because they naturally spread throughout the body, complicating targeted research efforts. Additionally, one significant limitation is the difficulty in humanizing the immune system within animal models. The immune response of mice doesn’t perfectly replicate how the human immune system reacts, making it hard to generate reliable data for human applications.
Scientists are now focusing on understanding the biomechanical properties of 3D cancer models to improve our comprehension of tumor behavior. A team from the Department of Biomedical Engineering at the University of Connecticut has developed a groundbreaking method to measure the stiffness of 3D spheroids using microtweezers. These microtweezers, created through 3D printing with nylon powder, feature a flexible plate spring, a bimorph piezoelectric actuator, and two cantilevers that act as force-sensing tips. Essentially, they work like a pair of chopsticks to compress and analyze the cancer organoid.
In their study, breast cancer cells were used to grow spheroids, that after five days, reached a diameter of about 200 micrometers. The Young’s modulus (a measure of stiffness) was calculated using simulations, where each spheroid was modeled as a sphere.
To investigate the structural significance of the ECM, Jaiswal et. al. pressed with the microtweezers treated five-day-old spheroids with collagenase, an enzyme that breaks down collagen, one of the primary ECM components. The results were striking: the treated spheroids had a significantly lower Young’s modulus compared to untreated samples. This clearly demonstrated the ECM’s role in maintaining structural integrity. By reducing the ECM stiffness, researchers can simulate environments with weakened structural barriers, enabling them to test how drugs penetrate softer, less resistant tissues. This approach provides valuable insights into how tumors with compromised ECM respond to treatment, potentially improving drug delivery strategies.
Therefore, by using 3D cancer models and mechanical testing, like microtweezers, researchers can understand the relationship between ECM pronunciation and tumor stiffness, allowing them to better understand how drugs will act in the presence or absence of these complex structures. This combination allows scientists to screen potential treatments in conditions that closely mimic real tumors, helping to predict drug effectiveness earlier and avoid costly animal trials. If you’re intrigued by biomechanics in general and the cutting-edge techniques scientists use to study it, check out our other blog posts for more fascinating insights.