2025 Trends: Organoids

Organoids exhibit various structural and functional characteristics of their in vivo counterpart organs and have led to many new cancer models. According to a report by The Insight Partners, the organoid market is expected to reach $15.01 billion in 2031, a CAGR of 22.1% over 2023’s $3.03 billion.

GEN talked to several R&D experts to get a sense of where the organoid market might be headed in the next few years.

Organoid Field Poised for Expansion

The failure rate of clinical trials is high, exceeding 85%, due to various reasons such as safety and efficacy concerns. Conventional methods of assessing drug properties involve animal models and 2D immortalized cell cultures, but they have limitations in capturing the species-specific nature of human diseases. Human organoid models have emerged as a promising alternative that better mimic many aspects of human physiology. In addition to their potential to serve as a bridge and a more cost-effective alternative to animal toxicity testing, organoids are increasingly used for disease modeling and orphan disease drug screening. The upcoming year may witness significant advances in several key areas related to human organoid models, including attempts to incorporate adult tissue-specific immune compartments, integration of organoids and organ-on-chips, routine automated multiomic characterization of 100s-1000s of organoids, and increased use of patient-derived organoids for personalized treatment.

Despite the promise of organoid models, several challenges remain. These include a lack of standardization, scalability, and limited physiological relevance due to missing tissue-specific cell types, including the lack of a microbiome and incomplete maturity/function. Complex cocultured organoids and assembloids generate intra-organoid heterogeneity and exhibit necrosis due to inaccessibility of nutrients as organoids grow in size. There is also a lack of reproducibility between organoids stemming from a lack of control over organoid shape, size, and cell type composition. Despite these challenges, the field is poised to expand ongoing efforts to integrate organoids and organ-on-chips for more reproducibility and scale-up, microfluidic architectures that connect different tissue organoids using circulatory mechanisms mimicking the human body, and the use of organoid cell atlases towards better standardization, as well as academia/industry partnerships in generating next generation automated solutions for high-throughput organoid generation and characterization. Finally, advances in the analysis of spatial biology datasets are expected to be deployed for faster analysis of 3D organoids.

Improving Drug Development by Incorporating Human Diversity

Drug discovery is at an important inflection point in its growth. Modern therapies are increasingly designed and tailored with the end in mind—humans. Advanced modalities, cell and gene therapy, and antibody approaches share common features of specificity towards mRNAs, proteins, or antigens of patients. As such, human in vitro models are critical to driving the momentum of next generation therapeutics, particularly in rare diseases affecting the central nervous system where every moment matters to deliver personalized treatment.

As a recognized alternative method to animal testing, organoids are redefining modern science through their ability to mimic the function, structure, and biological complexity of organs. Stem cells can be guided to self-assemble in 3D to generate organoids, small in vitro replicas of organs. By closely mimicking the heterocellular composition of the tissue of origin, organoids allow us to replicate the cell composition of an organ and the interactions between different cell type populations that are intrinsically interconnected. This enables the in vitro reconstruction of functional aspects of human physiology in a laboratory setting. By generating organoids from healthy and diseased donors, and individuals with varying genetic backgrounds, we can assess whether the same drug will display similar activity, or adverse effects, within a certain population.

One of the primary roles for organoids is to be an early predictor of a drug’s success or failure, which saves the client money and reduces downstream liability. The heterogeneity of the human population has never been considered in drug discovery, or at least only later at the clinical trial stage. With organoids, we can incorporate human diversity into the earliest stages of drug development, bringing the human component to the forefront of decision-making on whether a new drug candidate will progress further in the drug discovery and development pipeline. 

Patient Organoids for Personalized Medicine

Over the last two decades, utilization of organoids as model systems has been established in the scientific community, being recognized by Nature Methods as method of the year in 2017, and methods for modeling development, embryoids, again in 2023. These milestones capture the renewed promise of organoid technology for development and disease modeling that continue providing significant advances in the fields of personalized and regenerative medicine.

Furthermore, the passing of the FDA Modernization 2.0 Act empowers researchers to use innovative non-animal methods, including the use of organoids. The ability of such methods to accurately model human physiology could transform the speed and success of bringing safe and effective treatments to market.

To fulfill the promise of organoid applications in human healthcare, there are some needed improvements to facilitate scaling and advancing complexity of this model system. When scaling the quantity of organoids required for high throughput or regenerative medicine applications there are options to maintain consistent size for static expansion. Scaling organoids under dynamic conditions introduces complications including maintaining size consistency, optimizing gas exchange, and shear stress. There are recent bioreactor and encapsulation technologies that help address these challenges, but continued advances in GMP-grade extracellular matrices and encapsulation technologies must evolve to complement organoid scaling from static to dynamic conditions. This is essential to recognize the full promise of a high-throughput, consistent drug screening tool and for therapeutic applications involving regenerative medicine.

In parallel to these opportunities, another critical need is continued advancement with vascularized organoid models. Fully vascularized organoid models will generate a more complete understanding of drug delivery related to therapeutic efficacy. Additionally, regenerative medicine applications will benefit from this additional complexity while helping alleviate some of the challenges mentioned previously relating to optimizing gas exchange during expansion in dynamic systems.

Some of these improvements in vascularization have been realized through microfluidics platforms or organs-on-chip technologies. The current challenge is to scale these learnings to meet the needs of large-scale expansion.

Despite the current challenges, it is encouraging to see the speed at which innovation in the organoid space continues to advance within the broader research community. These advances have already impacted patients receiving benefits of personalized medicine through patient-derived organoids and we will continue to improve human healthcare as these advancements are realized. 

Integrating Organoids with Organ-Chips

Advanced in vitro models such as organoids and Organ-Chips have revolutionized the drug discovery and development process by providing robust models of human tissue structure and function. However, organoids face challenges such as variability in size and production, limited scalability, and the absence of immune cells and dynamic physiological cues. A significant limitation is the lack of polarity in organoids, which are traditionally basolateral-out, restricting direct access to the lumen and limiting their utility for studying drug absorption and host-microbiome interactions.

To fulfill their ultimate promise in human healthcare, efforts must focus on standardizing organoid generation processes and enhancing their reproducibility. Advances in cell sourcing, such as patient-derived stem cells, and streamlined methods for large-scale production are critical to address these gaps.

Integrating organoids with Organ-Chips offers a complementary solution, combining the three-dimensional structure of organoids with the dynamic functionality of Organ-Chips. Organ-Chips provide microenvironments incorporating fluidic flow and mechanical cues, enhancing cellular differentiation, well-polarized cell architecture, and tissue functionality. These combined platforms advance applications such as drug metabolism studies, infection modeling, and personalized medicine. They also enable co-culture with immune cells or microbes, allowing researchers to study complex interactions in diseases like inflammatory bowel disease or enteric coronavirus infection.

A critical trend is enhancing accessibility and scalability of these technologies for research and preclinical drug testing. Advances in Organ-Chip fabrication technology, coupled with improved cell sourcing, are integrating Organ-Chips with organoids, making them more practical for widespread use. By providing physiologically relevant models, these technologies are poised to reduce and replace animal testing, transform basic research, and improve drug discovery and development.

As organoid and Organ-Chip technologies evolve together, they offer transformative potential for advancing biomedical research. By unlocking new frontiers in human-relevant and ethical models, they pave the way for innovation in personalized medicine and beyond. 

Developing Validated, Trustworthy Models

A 2023 survey by Molecular Devices revealed that nearly 40% of scientists rely on complex human-relevant models like organoids, with their use expected to double by 2028. However, two significant challenges in complex cell model development were identified: reproducibility and batch-to-batch consistency. The 60 percent of scientists not yet working with organoids—but engaging with 2D human-relevant models like primary cells and induced pluripotent stem cells (iPSCs)—can certainly relate. Advances in automation and artificial intelligence (AI) have begun to address these issues successfully and we expect notable integration of these innovations into more laboratories this year.

Solutions combining the power of automation and AI to produce reliable human- relevant models in a more reproducible and efficient way than traditional manual approaches are vital. With this technology, researchers have the freedom to select their model of choice and the flexibility to optimize and set culture parameters to produce the desired phenotype. It eliminates the need for hands-on care of complex cell models, standardizes protocols to reduce variability, and removes human bias from decision- making, ensuring cells receive exactly what they need to consistently mature into reliable models.

We also anticipate a growing demand for assay-ready, validated models that have undergone rigorous testing and characterization, confirming they accurately and reliably mimic biological processes, behaviors, and responses of cells in living organisms. Our in-house scientists use proprietary processes to confirm model relevance and predictive value before they reach a researcher’s hands. Reproducible organoids allow researchers to get right into asking specific biological questions, conducting disease studies, or testing therapeutic compounds.

Researchers want trustworthy, human-relevant models. Integrating automation and AI into organoid development workflows—or opting for validated off-the-shelf models—are a few innovative and accessible ways to achieve this in 2025, especially when partnering with industry experts skilled in complex biology, automation, and data science technology. 

Realizing the Promise of Organoid Technology

Organoid technology is one of the most promising areas of research in the fields of regenerative and personalized medicine, as well as having enormous potential in drug discovery. However, there are limitations of the current organoid production and culture systems that have held them back from their potential. Overcoming these is the main current trend in organoids.

There are upper limits to the growth of organoids due to the need to diffuse nutrients throughout the entire structure, including the development of a necrotic core when a certain size limit is reached. The development of systems such as stirred bioreactors can help to improve diffusion and scale up production. Organoids may never be a high-throughput system, especially when considering patient-derived organoids (PDOs) with limited starting materials. But for some organoid types, bulk production could be useful to support medium-scale screening experiments. Technologies to analyze such experiments are also important.

There is also a lack of vascularization in the structures, which both limits organoid size and the relevance of some tests. We will see an increasing number of studies attempting to vascularize organoids (e.g., through co-culture with endothelial cells).

Relevance to mature organs and diseases presents a further conundrum. The fetal phenotype that arises from using induced pluripotent stem cells (iPSCs) is not always appropriate for studying adult diseases. PDOs or adult stem cells can address this to some extent but they come with the caveat of lower throughput.

Gene editing using CRISPR or a similar approach can introduce a disease phenotype into PDOs (e.g., studying tumor development). Furthermore, the cellular microenvironment can be fundamental to organ development or disease progression. Failing to include an appropriate extracellular matrix can be detrimental to studies. I foresee the development of recombinant and synthetic materials being another area of activity.