Organoid Technology

Adult Stemcells

The discovery of LGR5 as a specific marker of adult stem cell of the small intestine and colon by the group of Dr Hans Clevers was a turning point in stem cell research (Barker et al., Nature 2007). For decades scientist had been trying to discover the identity of 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 indebt understanding of the regulation of intestinal homeostasis and cancer allowed the group to definitively identify the stem cells in the intestine as LGR5 positive cells.

In the years following this seminal finding, Dr Clevers group  identified the stem cells in many other epithelial organs such as liver and 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 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-organization and expansion while maintaining 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 off spring (Sato et al Nature 2009; Gastroenterology 2011). The HUB Organoid Technology integrates this understand of the epithelial tissues of most organs into a method that combines long term in vitro expansion with direct representation of clinical responses of individual human patients to their treatment.

Applications of Organoid Technology

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

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

– In clinical development organoids serve as a model to guide further clinical trials and patient stratification, understanding of non-response, and as a biomarker or a tool to identify a molecular biomarker.

In addition, HUB Organoids are amendable to all normal laboratory experimental techniques such as gene editing, cryopreservation and can be easily manipulated. The Organoid models are highly robust and produce consistent results and therefore are applicable in basic, translational, and clinical research. The ability of 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 Biobanks Predictive Diagnostics Animal Derived Organoids

Pre-clinical

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

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

Clinical

The reason why individual patient, during a clinical trial of new treatments performed by pharma industry, respond or not to the treatment is almost always unclear. Only when very specific biomarkers are known do we have an indication why treatments are successful or not. Organoids can serve as the ultimate biomarker because they can be generated of each patient in the trial. In vitro tests of these patient organoids will demonstrate if the lab response correlates to the clinical response, successful or not. The organoid therefore will serve as a tool to identify the mechanism underlying success and failure and/or serve as a companion diagnostic in case of success if the treatment.

Organoid Biobanks

HUB has created Organoid biobanks from patient material that capture disease heterogeneity in diseases such as Cancer, Cystic Fibrosis and IBD. The biobanks are an expanding resource of highly characterized Organoids for different organ systems and include both genetic and clinical data of the patient.

Predictive Diagnostics

Clinical application of HUB organoids by generating organoids from individual patients provides a next generation tool for predictive diagnostics, designing targeted and personalized 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 trough put while maintaining in vivo relevance. In addition, to providing a direct comparison between animal and humans studies it will help decrease the use of animals in medical research.