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Key Applications of Organoids

by Rekha Pal, PhD, August 29, 2019 at 12:00 PM | Tags

graphic of organoid applications including drug discovery, toxicology, stem cell biology, regenerative medicine, studying disease mechanisms

graphic of organoid applications including drug discovery, toxicology, stem cell biology, regenerative medicine, studying disease mechanismsExplore the key applications of organoids, which are increasingly being used as in vitro models of human development and diseases, such as cancer.

The Need for Organoids in Research and Development

Improved preclinical models are needed for both basic research and drug development across a range of applications. Organoids (which we’ve discussed in detail in a previous post) have the potential to provide:

  • In vitro models recapitulating physiologically relevant 3D tissue architecture, which is known to influence therapeutic response.
  • In vitro models maintaining stable genomic and phenotypic profiles in long-term cultures (with passaging).
  • A platform for growing and propagating healthy cells in vitro without relying on viral transduction or transformation, which is key for studying basic developmental biology.
  • Preclinical models which are established quickly and cost effectively, and are amenable to large-scale drug screening.

Key Applications of Organoids

Organoids are now commonly used across a variety of research disciplines and applications, with studies and data extensively published. Here, we’ve summarized the main applications of organoids across a variety of research fields.

Developmental and Stem Cell Biology

As organoids are derived from stem cells, this positions them as valuable tools for studying complex developmental biology processes. This includes investigating the roles played by different morphogens and the processes that commit cells to a specific fate during early development.

Advances in recent years have led to protocols that allow for the long-term maintenance and expansion of organoids in vitro. Therefore, organoids are an ideal model to probe fundamental stem cell biology questions such as determining necessary signals to maintain cellular “stemness” or induce proliferation in different organs, and what the consequences are when these signals go awry.

Disease Mechanisms

Organoids are well known to have robust genomic and phenotypic stability. This stability preserves disease-relevant mutations over time during long term cell culture and in vitro expansion. Organoids are also relatively easy to manipulate using CRISPR/Cas9 or shRNA technologies. This allows researchers to examine the role of specific genes in disease pathogenesis.

Application Examples

  • CRISPR/Cas9 Genome Editing: CRISPR/Cas9 genome editing was used to correct a faulty CFTR gene in organoids derived from cystic fibrosis (CF) patients. The locus was successfully corrected by homologous recombination in the cultured intestinal stem cells. Notably, the corrected allele was fully functional, as demonstrated in clonally expanded organoids.

  • Gastric Development and Disease: Human gastric organoids helped to identify novel signaling mechanisms regulating early endoderm developmental events upstream of the transcription factor NEUROG3. They’ve also been used to better understand mechanisms of pathogenesis, which led to the discovery of a role for H. pylori infection in the activation of signaling and induction of epithelial proliferation.

Regenerative Medicine

Organoid transplantation in experimental colitis models proved that an intact intestinal layer can be reconstructed. When small intestinal organoids were transplanted in the colon, they successfully retained their original features, like villus formation and the presence of Paneth cells. This retention shows the phenotypic stability of cultured adult stem cell (ASC)-derived organoids.


Organoids are considered to be miniature versions of organs, and they often display a very accurate microanatomy. This makes them invaluable for in vitro modeling of drug adverse effects, specifically in organs commonly susceptible to drug-induced toxicities (i.e. gastrointestinal tract, liver, kidney). This in vitro data complements data from in vivo studies.

Application Example

  • Nephrotoxicity: Human kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells have been successfully generated. Using this model, cisplatin was confirmed to be nephrotoxicant, suggesting that organoids can be used for nephrotoxicity screening.

Infectious Disease

Organoids have facilitated studies on interactions between the gastrointestinal tract and enteric viruses. For instance, gastric organoids were used to show the pathophysiological response of gastric tissue to H. pylori infection.

Since organoids represent all components of the original organ, they’re suitable models for studying infectious diseases, such as respiratory syncytial virus (RSV) with human lung organoids and hepatitis B virus (HBV) with human liver organoids.

Drug Discovery

Organoids are highly useful in drug discovery due to their relative ease of establishment and expansion in vitro. Organoids can be grown with high efficiency from both patient-derived healthy and tumor tissues. This allows side-by-side comparison of drug response between organoids from the same patient, and allows researchers to ask patient-specific pharmacological questions.

Application Examples

  • Cancer: Organoids can be established from human cancer biopsies (commonly referred to as tumor organoids), which faithfully recapitulate a patient’s cancer in vitro. Alternatively, healthy organoids can be efficiently transformed by inducing gene mutations in key cancer pathways. These two approaches provide avenues for organoid applications in personalized medicine and the investigation of cancer mechanisms, respectively.

  • Large-Scale Efficacy Screens: Tumor organoids are predictive of patient drug response, with validation studies recently published using tumor organoids derived from cancerous colon and bladder tissue.

    • Importantly, tumor organoids accurately reflect intra-tumor and inter-patient heterogeneity. For drug efficacy testing, tumor organoids are therefore derived and expanded to large scale from different regions of the same tumor and various patients with the same disease. This means organoids provide a key platform for drug development and evaluating personalized in vitro drug response.

  • Immuno-oncology (I/O): As discussed in a previous post, optimized protocols by Hubrecht Organoid Technology (HUB) have been key to the overall increase in organoid use. HUB has also established co-cultures of patient-derived organoids (PDOs) with either autologous or engineered immune cells. This co-culture technology is used to screen the efficacy of I/O compounds or engineered T cells.

    • Additionally, an air-liquid interface system to propagate PDOs and mouse tumor-derived organoids was recently published. When the organoids were transplanted into syngeneic hosts, they showed native embedded immune cells (i.e. T, B, NK, macrophages). Sophisticated sequencing techniques also showed that PDO tumor-infiltrating cells accurately preserved the original tumor T cell receptor spectrum. Finally, the PDOs displayed cytotoxicity profiles similar to those in patients treated with immune checkpoint inhibitors, such as anti-PD-1 and /or anti-PD-L1.


Compared to traditional in vitro culture models, organoids represent a superior approach for modeling human developmental biology and diseases. By taking advantage of the fact that they accurately reflect the structure and function of the organ they were derived from, researchers are exploiting organoid use across a wide array of applications.

webinar on applications of tumor organoids in oncology drug discovery


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