Organoid Technology

Adult Stem Cells

The discovery of LGR5 as a specific biomarker of adult stem cells in the small intestine and colon by the Clevers group was a turning point in stem cell research (Barker et al., Nature 2007). For decades scientists had been trying to discover which cells were the stem cells in adult solid organs.

Although their existence had been accepted for at least 50 years, their identity remained obscure. Novel mouse genetic technology combined with an in-depth understanding of the regulation of intestinal homeostasis and cancer allowed the group to definitively identify the LGR5 positive cells as the stem cells in the intestine.

In the years following this seminal finding, the Clevers group identified the stem cells in a number of other epithelial organs, such as the liver and the pancreas. These discoveries greatly increased our understanding of stem cell regulation, tissue homeostasis and repair, as well as diseases such as cancer. In addition, the finding opened up an array of new opportunities for regenerative medicine.

Patient-derived Organoids

The breakthrough of the Organoid Technology invention is the ability to establish a laboratory model of any epithelial disease from any patient, a “Patient in the Lab”. HUB Organoids are capable of self-renewal, self-organisation and expansion while maintaining their genetic and phenotypic stability. These features make HUB Organoids exhibit organ functionality recapitulating the tissue of origin.

Our understanding of adult stem cell biology allowed us to identify the specific regulatory pathways that are essential for in vitro expansion of stem cells and their offspring (Sato et al., Nature 2009; Gastroenterology 2011). The HUB Organoid Technology integrates this understanding of the epithelial tissues of most organs into a method that combines long-term in vitro expansion with the direct representation of clinical responses of individual human patients to their treatment.

Applications of Organoid Technology

The technology allows for fundamentally new approaches to pre-clinical drug development, patient stratification and predictive diagnostics.

– In pre-clinical drug development, a model that is directly representative of a patient’s clinical response is ideally suited to combat the high attrition rate in drug development due to existing pre-clinical model systems lacking patient relevance.

– In clinical development, organoids serve as a model for guiding further clinical trials and patient stratification, for understanding non-response, and as a biomarker or a tool for identifying a molecular biomarker.

In addition, HUB Organoids are amendable to all normal experimental techniques used in the lab such as gene editing, cryopreservation and they can be easily manipulated. The organoid models are highly robust, produce consistent results and can therefore be applied in basic, translational, and clinical research. The capacity for long-term expansion allows for use in prolonged studies at significantly lower costs than primary cell systems of patient-derived samples.

Pre-clinical Clinical Organoid Biobank Predictive Diagnostics Animal Derived Organoids

Pre-clinical

Drug discovery platform: HUB Organoids serve as an ideal platform for drug discovery screening, target discovery, and genomic and functional studies on a scale that could never be achieved for clinically relevant models.

Drug development: HUB Organoids provide drug efficacy, safety and mechanistic data. Furthermore, disease-specific collections of organoids enable pre-clinical stratification of patient populations.

Clinical

During clinical trials of new treatments carried out by the pharma industry, it is almost always unclear why an individual patient responds or doesn’t respond to the treatment. It is only when very specific biomarkers are known that we have an indication of why treatments are successful or not. Organoids can serve as the ultimate biomarker because they can be generated from each patient in the trial. In vitro tests on these patient organoids will demonstrate if the lab response correlates to the clinical response, successful or not. The organoid therefore serves as a tool for identifying the mechanism underlying success and failure and/or serves as a companion diagnostic in the event that the treatment is successful.

Organoid Biobank

HUB has created an organoid biobank from patient material that captures disease heterogeneity in diseases such as cancer, cystic fibrosis and IBD. The biobank is an expanding resource of highly characterised organoids for different organ systems and includes both the genetic and clinical data of the patient.

Predictive Diagnostics

The clinical application of HUB Organoids by generating organoids from individual patients provides a next generation tool for predictive diagnostics, designing targeted and personalised therapies as well as clinical patient stratification.

Animal Derived Organoids

Organoids derived from mice, rats, dogs, and mini pigs allow for in vitro toxicology and research that will provide high throughput whilst maintaining in vivo relevance. In addition to providing a direct comparison between animal and human studies it will help decrease the use of animals in medical research.