The way we currently test and validate drugs is highly inefficient. It requires a lot of money and takes a lot of time and that is why a drug takes 10-12 years to come to the market. This causes global suffering of people where patients with serious illnesses cannot get any treatment for them. Cancer, which is a leading cause of death worldwide, claims 10 million lives per year! The problem is pretty evident, the current tools that are employed for drug testing and validation are outdated. As the field of medicine and research evolves, there is an urgency to replace these tools with a newer one. The ideal tool should be sustainable, which means it can validate several drugs with ease, be cost-effective, and most importantly should produce reliable results. One such innovative technique is 3D culture, which is slowly moving up the ranks to become the gold standard for drug testing, and rightly so because it overcomes the limitations of the traditional tools in use.
Currently, 2D cultures and animal models are at the forefront and are the main tools for drug-based investigations. The major issue with these tools is that they generate results that are unreliable and unpredictable. 2D cultures are human cells grown in dishes in the laboratory. They do not represent how cells behave and function like they do inside the body, which leads to inaccuracy. Whereas, animals are unpredictable because they process chemicals differently compared to humans. An ideal analogy would be to conclude that chocolates are toxic to humans just because they cause severe illness in dogs. The statistics of preclinical studies amplify the limitations of these tools – only 9.6% of drugs that enter phase I of clinical trials come to market. That means ~90% of drugs that pass preclinical studies on animals and 2D cultures fare poorly when tested on humans. They are not effective and not suitable to assess safety and toxicity of a drug. These not only make the patients suffer more, but also affect healthy individuals too as clinical trials are done on patients and healthy individuals too.
The concept of ‘home away from home’ was the main reason Airbnb grew into a multibillion-dollar business. It provided travelers places to stay that felt just like their homes. 3D cultures are Airbnb equivalents to cells because they provide an environment just like the inside of the human body. Cells cultured in 3D retain the cell-cell and cell-environment connection which makes it a model having goodness of both 2D cultures and animal models. There are basically two broad ways of developing 3D cultures: scaffold-based or scaffold-free 3D cultures. Scaffolds are biocompatible support structures designed to facilitate growth of cells. They can also be modified in a way that they recreate an environment similar to in vivo. You can read more about this here. Both these systems have their pros and cons and their usage depends on the application. Spheroids are 3D cultured structures that are developed with a scaffold-free approach. They are formed by aggregating single or multiple cell types by simply sticking to each other. These simple structures are miles ahead of 2D cultures and suitable for screening drugs. They are also a great tool to test novel drug delivery methods. At the nanomedicine research group, we employed lung cancer spheroids to evaluate an innovative nanoparticle based drug delivery approach. The limitation while working with spheroids is that they do not self-assemble and do not have the capacity to regenerate which means they cannot be stored for a long period of time as the cells cannot be maintained viable.
Another prominent 3D culture structure is ‘organoids’ which are cells grown in 3D using a scaffold. Unlike spheroids, organoids are developed by using stem cells that divide and generate organ-specific cells by following the internal development blueprint. This makes organoids more organ-like models because they have accurate microanatomy like the parent organ. The role of scaffolds is to provide physical and chemical cues to stem cells so that they develop in a desirable organ of choice. Organoids are self-assembling miniature representations of parent organs that are beneficial to researchers. For example, brain organoids can provide important insights to understand diseases in the brain. With the inherent power to regenerate thanks to stem cells, organoids can be stored for a longer time. Similar to organoids, there is a particular 3D structure that has greatly benefitted cancer researchers. Tumor-like organoids or tumoroids are developed using cancer cells derived from cancer patients and grown using appropriate scaffolds. They are employed to better understand a cancerous tumor in the lab.
Tumoroids make it possible to understand how the environment around a tumor influences the behavior of the tumor. Also, tumoroids accurately mimic the in vivo characteristics of the tumor, the complexity and heterogeneous populations of cancer cells. This makes it a great invitro tool to understand heterogeneity of cancerous tumors. These characteristics of tumoroids help researchers understand mechanisms of cancer onset and growth. This could lead to development of novel therapies against drug resistant tumors and devising new delivery approaches. In the future, tumoroids have a massive potential for development of precision medicine. As cells are derived from the patient, researchers can evaluate and formulate specific treatment options for the patient.
Significant advancements and developments in the field of 3D culture are going to be crucial for the evolution of modern medicine. Current and potential applications of 3D culture makes the future of therapeutics and drug development promising. Learn more about the recent research and technological developments in the field of organ on a chip at 3D cell culture workshop 2022. Register today at https://forms.gle/j358V2cn2dKtZJqb9
References:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609997/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564148/
https://pubmed.ncbi.nlm.nih.gov/34427389/
Image references:
https://hsci.harvard.edu/organoids
Written by: Parth Choudhari – Science Communicator, Nanomedicine Research Group.