DDW Editor Reece Armstrong learns about Molecular Devices’ Organoid Innovation Centre (OIC) and how the company is aiming to advance research into 3D biology and organoids.
In April 2021, life sciences solutions provider Molecular Devices launched its Organoid Innovation Centre (OIC), an initiative designed to help scientists leverage the potential of 3D biology throughout the drug discovery process.
Here, DDW’s Reece Armstrong speaks to Dan O’Connor, VP of drug discovery at Molecular Devices, about what the OIC offers to pharmaceutical companies and the advantages and barriers of 3D biology.
2D vs 3D
2D biology has been used by pharmaceutical researchers for decades. Think of a cell culture, where scientists can observe the growth of a cell in the body in an in-vitro setting, and gain an understanding of how they react to different drug compounds. Researchers use this type of biology to understand the mechanisms of disease and even to diagnose a patient’s disease through the use of tissue growth and technologies such as fluorescence microscopy, to gain deeper understanding into the molecular make-up of a cell.
2D biology, whilst widely used and relatively inexpensive does have its disadvantages however. For instance, 2D environments such as cells grown in a petri dish aren’t representative of how cells actually work and interact with each other in the body. Therefore, while researchers can understand just how a drug molecule impacts a cell, they can’t be sure that it will perform the same when used in-vivo.
The benefits for 2D biology however, are that it’s been used for decades, meaning there is a wealth of comparative literature to inform drug discovery research along with longstanding industry expertise.
3D biology is less common throughout the industry but is starting to make headway due to the benefits it offers scientists. One of these benefits is how cells grown in this type of culture are able to interact with their surroundings, similar to how they would perform in-vivo. It’s hoped that through this, scientists will be able to better predict how drug molecules perform in the body, leading to expedited drug development and better outcomes for patients.
The OIC
Molecular Devices launched its OIC with the goal of advancing scientific research into 3D biology. One of the goals was to include systems that would help companies overcome common barriers associated with automated organoid culturing and screening.
Since its launch the OIC has worked with over 30 customers and has developed more than 35 protocols for organoid development, handling, and analysis that cover a significant part of 3D workflows.
According to O’Connor, the company began exploring more of the 3D biology space when customers began enquiring about organoid models around five years ago. Organoids are developed using pluripotent stem cells (PSCs) or adult stem cells in a 3D culture matrix, and mimic organs in the human body.
As a technology, organoids are still relatively young – O’Connor puts them at around a decade old – but the promise they present means that interest in them has grown. “About five years ago customers started enquiring about wanting to do organoids which were a relatively new concept. We started to see this spike in interest in organoids, so we did a market study and a common theme was really around pain points of consistency and stability when growing organoids,” O’Connor says.
On the point of consistency, the fact that organoids are a relatively new technology means that there isn’t a set ‘baseline’ in how companies grow them, with the differentiation potentially affecting research undertaken with them. “One of the biggest pain points is really the consistency of organoids. That means if two pharma companies are trying to grow say a cardiac organoid, they won’t be consistent across the board,” he says.
According to O’Connor, removing these pain points such as consistency will help the whole field move forward so that researchers can grow organoids in any lab anywhere in the world.
Of course though, the move from 2D to 3D biology isn’t easy. “It’s a very complex biology workflow,” O’Connor says. “2D cell culture has been around for many years. But 3D cell culture is much more challenging. You have many more steps, it’s all about precision timing of adding growth factors and if you don’t get that timing down exactly right, and there’s little nuance to that, your cells might not differentiate correct, you might not get the intended organoids to the consistency that you ultimately want to see and get. That pain point right there needs to get resolved in order for this to go mainstream.”
To solve this problem and to enable scientists to really be able to access organoids as a tool for research, the OIC is using a workflow solution that is entirely automated. “The tool is a fully automated, integrated workflow that you can generate organoids as a walk away solution from start to beginning,” O’Connor says.
This automated approach allows collaborators to access a 3D workflow, from the 2D pre-culture stage all the way to organoid growth and then analysis, and even check in on the whole process remotely. Whilst the OIC could be mistaken for a kind of contract research organisation (CRO) set-up, where work is outsourced to Molecular Devices for a fee, this isn’t the direction the company wanted the centre to take.
Instead, Molecular Devices wants to use the centre to advance the science surrounding organoids through collaborations with its customers. “We wanted to use it as a tool to collaborate with all types of customers,” O’Connor says, “[from] academic, government, pharma, to biotech – and it has ranged from start-ups all the way to the largest pharma companies in the world. It’s such a developing and newer concept of growing organoids and doing cell engineering, to then do drug discovery with those organoids. There are several different directions we can go with this but one of the main stays with this is to keep it as a resource for our customers.”
As the science evolves and Molecular Devices gains a better understanding of using organoids as research models, the company hopes that this translates into better and more efficient drug discovery and development. O’Connor says that “3D organoids are more physiologically relevant than 2D models,” and there is data which supports this.
“There’s data that show if you use organoids [in a clinical trial] the drug that works nine out of 10 times on the organoids will work nine out of 10 times on the patients and vice versa.”
The benefits to drug development are obvious then. A new drug can cost an average of $1 billion to bring all the way to market so having better physiological models which can indicate how a candidate will work, with more accuracy, compared to 2D models, should bring about savings in terms of cost and time.
As with any emerging or promising technology one of the things that can be difficult to gauge is just how widely adopted it is within the industry.
For O’Connor and Molecular Devices, that’s the kind of data they’re still trying to gather. For O’Connor, one of the questions he’s trying to answer is just what it will take for a company like a big pharma organisation to transition from 2D biology to 3D. “We feel that removing the barriers and pain points will give the Pfizer’s of the world that reason why to translate 2D to 3D. The data shows it should be faster and cheaper,” he says.
Covid-19
The OIC launched in the middle of the Covid-19 pandemic and its development was no doubt affected by the global crisis. O’Connor admits that opening up an innovation centre at this time was “a little scary” but that the impact of Covid-19 on life sciences companies really acted as a catalyst into helping Molecular Devices pursue this area of research.
“The overall response to Covid-19 in the scientific community has been nothing short of amazing right?” O’Connor says. “Everyone gathered around and said we need a lot of funding to pull this off and we need to figure out how to be super-efficient in vaccine production etcetera.”
Whilst O’Connor admits it was scary to open the OIC in the middle of the pandemic, the company “felt confident that the scientific community was willing enough to move this research forward.”
And from the perspective of Covid-19, O’Connor says that the scientific community’s interest in things such as antibody discovery, gene editing, and synthetic biology, played a role in helping shape the direction of the OIC. These are technologies that Molecular Devices is now adding to the OIC, alongside cell line instruments for synthetic biology so the OIC can engineer organoids in one workflow.
When asked whether these capabilities were added in direct to response to Covid-19, O’Connor says that “it was part of the justification,” of the OIC and in the company’s original plans for the centre.
The response to the OIC’s initial plans of having a centre for organoid growing and screening was amazing, O’Connor says, and enabled the company to begin its next phase of adding the biopharma technology into the OIC’s workflow.
Current research
With 3D biology offering potentially more benefits to drug researchers compared to 2D biology, the question arises just what areas of disease are currently being driven by the likes of organoids. “We’ve identified four 3D organoid models that we feel encompass 80% of what everyone is doing. We’re trying to be forward future looking as well around what researchers will be doing in three to five years,” O’Connor explains.
For now though, O’Connor says that the OIC is largely focused on gut, cardiac, brain and tumouroids. Research into tumouroids is an area he’s particularly excited about.
“The benefit with tumouroids is they’re fast growing. From a drug discovery standpoint that can be very impactful cause you can speed up your process significantly. There’s also an aspect of precision and personalised medicine with tumouroids – taking patient-derived cells and then growing many different mini tumouroids from a patient, and then running a panel of drugs to find which drug compound is going to work the best for this phenotype of tumour. That is very impactful right cause you’re getting a huge swathe of cancer therapies and immunotherapies with cancer. I think tumouroids have the potential to be absolutely enormous,” he says.
In science and particularly the pharmaceutical industry, the possibilities that technology represents and then how it is applied within the healthcare system is something that can be incongruous with each other. For the concept of screening compounds against a tumour sample to find out what drug is going to work, O’Connor believes the ultimate goal is to get “this type of process into the clinic.” But how do you translate the type of research taking place at the OIC into the clinic? “You need to generate the data first to really get the proof- of-concept that says yes these 3D models are the way to go,” O’Connor says.
O’Connor hopes that in the future, places like the OIC will have the ability to “fingerprint cells” and basically be able track them throughout their development as an organoid, so they can be sure that cells retain their same biological profile as when they first started out.
“Once that happens that opens the way to clinical,” O’Connor says, explaining how the OIC could have an integrated system of smaller platforms that constitute a full workflow and which allows a clinician to take patient data and cells and use them to create an organoid, on which to run a panel of drugs to determine which one works best against a tumour or a strain of disease. Right now, O’Connor says those capabilities aren’t available yet but he’s certainly excited about the potential the future holds for these technologies.
Competitive technologies
As it stands, one of the main technologies that runs parallel to organoids are organ-on- a-chip (OoC) platforms. OoC technology uses microfluidics to create a cell culture device that is representative of human tissues and organs working in vitro. A steadily emerging technology, OoC platforms have been used to predict the response of drugs and have applications similar to those of organoids of 3D biology.
O’Connor brings up OoC technology because he thinks it is often conflated with organoids and that the technology has its limitations. “Folks think that organ on a chip is all encompassing and it’s definitely not. The original idea behind organ on a chip was brilliant but the actual execution is much more challenging,” he says.
O’Connor agrees that having the idea of a whole body on a chip is a great concept since it can help researchers understand how a drug is metabolised throughout the body – whether it is toxic or not once it passes through the liver and into other organs for instance.
Right now, “there’s no other good way to do that,” O’Connor says, “and that’s why they use animal models to see how the liver metabolises the drug and what downstream effects occur.”
The ultimate goal for the industry is to get rid of animal models so it’s unfortunate that O’Connor says that scientists have yet “to pull off a whole body organoid type of chip.”
Instead, OoCs are developed as singular organs a lot of the time and are used as a way to test whether a drug will be toxic in the body. O’Connor believes that whilst there’s utility in this approach, the biggest impact will be through “self-organising organoids” that can be used to advance drug discovery and workflow, alongside toxicity testing.
Included in the DDW Synthetic Biology eBook, sponsored by Evonetix
Biography
Daniel O’Connor is Vice President of Drug Discovery at Molecular Devices specialising in high-content imaging technologies for screening 2D and 3D cellular disease models. With over 20 years of industry experience, he has developed an application-focused approach to drive innovation and advance customer solutions. He earned a BSc in Neuroscience from University of Minnesota-Twin Cities.
