Organoids: More than tissue culture and not less than animal models!

Karthic A

Inventing or discovering a new medicinal drug takes an average of 10 years from mind to market. It is due to the extensive regulation involved in assessing the safety and efficacy of any new active pharmaceutical ingredient in its administrable form. 

As part of drug testing, pre-clinical studies are conducted to ensure the drug’s safety and potential for treating medical conditions. These results are important when applying for a  new investigational drug application, based on which regulatory agencies approve its further development. Traditionally, pre-clinical research only involves in vitro and in vivo studies on cell culture and animal models, respectively. 

Cell culture-based studies just give a preliminary evaluation as they lack biological complexity and are very dissimilar to how cells exist in a real human being. Even though animal models like rats and mice can give better testing results, multiple drugs that successfully cleared animal testing failed in human testing as they were toxic to the liver.  It is primarily because the animal models are genetically, physiologically and metabolically distinct from humans. 

To improve the safety and suitability of drugs in humans, it is paramount to use more human-relevant models in the drug discovery and testing pipeline. Understanding this fact, researchers and firms all across the world are developing and switching towards human-relevant research focusing on the use of models like organoids, organ-on-chips,  3D bio-printed tissue and systems biology tools to mimic human responses. 

Considering the relevance of these advancements and the capacities of organoids, the  United States Food and Drug Administration has now announced that animal model studies are no longer required for new drug applications. 

Why did they do so? 

Organoids are three-dimensional multicellular constructs that mimic the structure and function of specific organs or tissues in the human body. They are generated from stem  cells or tissue-specific progenitor cells and can self-organise and differentiate into different cell types, forming complex structures similar to mini-organs. Hence, they overcome the lack of extracellular matrix interactions in 2D cell culture and the physiological differences in animal models.

Organoids provide a powerful tool for studying human diseases in a more relevant and controlled environment. By deriving organoids from patient-specific stem cells or introducing disease-specific genetic modifications, researchers can model and study various diseases, including genetic disorders, infectious diseases, and cancer. 

Organ-on-chips take this a step further by incorporating microfluidic systems that replicate the dynamic conditions and interactions between different organs in the human body.  These models provide more accurate representations of human physiology, enabling researchers to investigate drug responses, disease mechanisms, and personalised medicine approaches. 

Therefore, improved physiologic representation, high-throughput screening and modelling of human organogenesis and disease development encourage the usage of these cutting-edge tools in pre-clinical research and beyond. Over the years, many organisations, including the Centre for Predictive Human Model Systems, have continuously established the relevance and superiority of organoids and organ-on-chip in human-relevant research. It is time for us to embrace the new and move ahead.