Organoids & Organ-on-Chips: From Research Tool to Biomedical Application 

Hopefully soon, miniature versions of human organs will be the gold standard in personalized medicine and the discovery of new drugs. A few challenges remain, but these can be solved with cutting-edge technology. This is the takeaway from a recent workshop in Switzerland that brought together organoid experts from research, biotech, and pharma.

Imagine this: You receive bad news—cancer is spreading in your body. With cells from a biopsy sample, a robot immediately starts to cultivate hundreds of mini versions of your tumor. Each of these so called tumor organoids is then exposed to a different anti cancer drug regimen. An imaging system paired with artificial intelligence tracks the fate of each organoid and identifies the most effective treatment. A few weeks after your diagnosis, you receive a personalized therapy custom designed for your tumor. No need for multiple exhausting (and expensive) treatments with less potent drugs.

Brilliant ideas to improve medicine

Unfortunately, this scenario is just a fantasy for now. As pilot studies have shown, the method is feasible but not quite ready for standardized and widespread clinical use. For example, it takes more than six weeks to run the assays. The same is true for other applications proposed for organoid technology: regenerative medicine wants to use it to engineer replacements for damaged organs and tissues. Pharma companies intend to establish organoid platforms for large scale screens to discover better drugs. Organoid assays could also help to perform safety and toxicity tests, thereby speeding up regulatory processes and reducing reliance on animal models.

Organoids made their debut almost two decades ago when researchers found a way to coax adult stem cells into various types of human tissue. The differentiated cells self organize into 3D miniature versions of human organs like the brain, small intestines, or liver—most of the time under a millimeter in size. The mini organs can now be produced for almost any type of tissue. They have been a huge success in research because they mimic the physiological conditions in the human body much better than two dimensional tissue cultures or even animal models.

Scaling up through automation and digitalization

The presentations at a recent workshop in Switzerland (see below) confirmed the huge progress made towards the biomedical application of organoids. They also offered a glimpse at the cutting edge technologies that are currently being developed to overcome remaining obstacles. “One of the big challenges is the scalability and reproducibility of organoid protocols,” says Magdalena Kasendra, Director R&D at the Center for Stem Cells and Organoid Medicine at Cincinnati Children’s Hospital Center. At the workshop, she presented her team’s push to customize organoids for drug discovery and personalized therapies.

Especially if done at large scale, the production, maintenance, and quality control of organoids is extremely laborious and time-consuming. “A lab technician can classify less than 400 organoids a day,” says Lucie Jandet, COO of CSEM spin-off Visienco. Her company has developed an automated organoid sorter that uses bright-field imaging and artificial intelligence (AI) to classify over 3,000 organoids a day. The automation not only saves time, the robots also handle the fragile organoids more gently.

Other biotech companies at the workshop presented a variety of automated solutions to handle organoids. The systems can monitor growth, change the culture medium, control aeration, and perform image-based or biochemical assays. Conveniently, they are usually compatible with standard labware like 24- or 96-well plates. Deep learning and AI help to analyze the huge amount of data points collected. Most companies have several organoid systems and assays established but are open to develop customized solutions for new partners.

Microtechnology for multi-organ-systems

Another focus of the organoid community is the creation of organoid environments that mimic human physiology even better. In the body, all organs and tissues are connected to each other, e.g., through the circulatory system. Also, the cells of the immune system pervade many tissues, including tumors. Many companies and scientists have been successful in cultivating organoids that are vascularized and perfused with immune cells.

A promising way to simulate the interactions is the use of microtechnology and microfluidics to produce so called organ on chips. For this, organoids from different tissues are placed in tiny chambers on microchips and hooked up to each other with microchannels for perfusion. Various sensors can be integrated to monitor the system. For instance, one microchip presented at the workshop included lung, liver, and lymph node organoids that interact with each other in a near physiological way. In Europe, the UNLOOC consortium with 51 partners including CSEM, is driving the organ on chips technology forward for disease modeling and drug testing.

Pharma is on board

A clear signal that organoids have made the jump from research lab to the pharmaceutical industry is a 2022 decision by the U.S. Food and Drug Administration (FDA) that allows organoid models for preclinical drug efficacy and safety tests. It is hoped that this might improve the high failure rate of new drugs: Sixty percent of phase I and II clinical trials are terminated due to lack of efficacy, 30 percent because of toxicity.

Workshop presentations by pharma representatives confirmed that the pharma industry is committed to organoid technology. For example, Katie Kubek, Principal Scientist at Novartis, explained how intestinal organoids might be used to predict gastrointestinal adverse effects of drugs. “Organoid models bear the opportunity to be more effective, more human relevant, and in the end bring better drugs faster to the patients,” says Adrian Roth, Principal Scientific Director Precision Safety, Product Development Safety at Hoffmann-La Roche.