3D Organoids: The Invaluable Tool

By Kinda Al Koudsi


Cancer Around the World
The number of cancer patients globally is rising, and specific cancer indications have high mortality rates. For example, Breast cancer is the most prevalent cancer type in women, and the leading cause of cancer-related mortality.1 Cancer research employs a range of in vitro and in vivo models. One of the most demanding challenges of oncology remains the cost and time required to produce effective medicines. In fact, the probability of approval from pre-clinical development to phase I clinical trial for oncology drugs is 7%, which is lower compared to drugs for all other uses.2 Better pre-clinical tools for drug screening are desperately needed because of the high cost, unforeseen toxicity, and time-consuming nature of oncology drug production.

Studying Tumor Pathology

The most commonly used in vitro model for studying tumor pathology is the cultivation of tumor cell lines in two-dimensional (2D) models. This system, however, is unable to mimic the microenvironment of native tumors, which grows in three dimensions (3D), and does not adequately model all facets of tumors.3 Three-dimensional in vitro models has been increasingly used to overcome these limitations as they are more effective than 2D-cultured cells in simulating key tumor behaviors in vivo, such as hypoxia, dormancy, anti-apoptotic traits, and drug resistance4. The main advantage of 3D models is the ability to observe and reproduce the interactions between tumor cells and the extracellular matrix, and the interactions between tumor cells and the stroma, leading to maximized cellular communication and signaling. Furthermore, depending on the type of experiment, 3D cultures can have varying complexities.  They range from a basic cell spheroid model to complex tissue-engineered constructs, including organ-on-a-chip and microfluidics, which are now becoming useful tools in tumor cell biology studies.

The number of studies based on 3D cell culture models has notably increased in recent years (Figure 1). According to a survey conducted by HTS technologies HTS technologies, 70% of the researchers polled aim to shift from 2D to 3D cell culture, with many already did so. The more researchers turn to 3D cell culture, the faster new methodologies can be created to grow the organoids' promising future and address the existing limitations.

 

Figure 1: The number of publications per year (1968–2020) on 3D cell cultures (PubMed), retrieved from Jensen and Teng 2020.


3D Cell Culture 
With the use of organoids, 3D cell culture offers new methods to evaluate organ activity and potentially close the gap between 2D cell culture and animal models 5. Furthermore, 3D models can help reduce and replace the use of animals in research to address ethical issues and costs. Additionally, 3D cell cultures yields better and more realistic outcomes with a more precise depiction of human tissue, which accurately capture drug side-effects such as liver toxicity.6

This approach has a lot of room to grow in drug development, personalized medicine, disease modeling, stem cell utilization, organ transplantation, and toxicity tests for a variety of diseases including cancer, fibrosis, cardiac diseases, and neurological disorders (Figure 2).

Figure 2. The applications of the 3D organoid in drug development. Retrieved from Corrò et al. 2020.

References:

  1. Anastasiadi, Z., Lianos, G. D., Ignatiadou, E., Harissis, H. V., & Mitsis, M. (2017). Breast cancer in young women: an overview. Updates in surgery69(3), 313-317.
  2. Hay, M., Thomas, D. W., Craighead, J. L., Economides, C., & Rosenthal, J. (2014). Clinical development success rates for investigational drugs. Nature biotechnology32(1), 40-51.
  3. Lovitt, C. J., Shelper, T. B., & Avery, V. M. (2014). Advanced cell culture techniques for cancer drug discovery. Biology3(2), 345-367.
  4. Imamura, Y., Mukohara, T., Shimono, Y., Funakoshi, Y., Chayahara, N., Toyoda, M., ... & Minami, H. (2015). Comparison of 2D-and 3D-culture models as drug-testing platforms in breast cancer. Oncology reports33(4), 1837-1843.
  5. Jensen, C., & Teng, Y. (2020). Is it time to start transitioning from 2D to 3D cell culture?. Frontiers in molecular biosciences7, 33.
  6. Kim, J., Koo, B. K., & Knoblich, J. A. (2020). Human organoids: model systems for human biology and medicine. Nature Reviews Molecular Cell Biology, 21(10), 571-584.