Unlocking The Full Potential of Organoids
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Organoids are becoming an increasingly popular research tool, both in drug discovery and diagnostics. These ‘mini-organs’ are defined by Lancaster and Knoblich “as containing several cell types that develop from stem cells or organ progenitors and self-organize through cell sorting and spatially restricted lineage commitment, similar to the process in vivo.”
However, before the full potential of organoids can be realized, a number of obstacles must first be overcome, including optimizing the conditions they are grown in. To learn about the importance of the extracellular matrix and how it can be harnessed to improve organoid culture, we spoke to Colin Sanctuary, CEO and founder of QGel, a spin-out from EPFL.
Anna MacDonald (AM): Can you tell us about the extracellular matrix (ECM) and some of the roles it plays?
Colin Sanctuary (CS): The ECM is the material between cells present within all tissues and organs. It provides the microenvironment required for proliferation and differentiation of the specific cell type it surrounds. Given that the human body is made up of 200 different types of cells, each with a specific function, the composition of the ECM must vary between tissue types to support the needs of that tissue. For a long time, scientists have neglected the matrix material, which is arguably just as important as the cells themselves to build organ like structures ex vivo. Changes in the conditions of the ECM, such as the type of growth factors or the concentration of hormones, inevitably affect cell behaviour and can determine the healthy or diseased state of those cells. Ultimately, one can promote or even inhibit disease progression through a precise fine-tuning of key characteristics of the ECM.
AM: What are some of the limitations of current organoid culture systems?
CS: Organoids are miniature organs grown in vitro that are able to maintain the key physiological features of the patient’s tissue. Unlike simple cell cultures, they self-organize and grow to retain structural and functional properties of the organ they are derived from. Until recently, scientists have been growing organoids in animal-derived extracellular matrixes where the composition is undefined– which presents a series of inherent obstacles. First, because animal-based gels lack a defined set of components, they cannot be manufactured on a large scale without batch-to-batch variability, something that is essential for drug development. Secondly, and linked to the first issue, is that synthetic compositions are required for use with large-scale robotic drug screening equipment. Third, animal-derived matrixes bring about ethical implications of sacrificing large numbers of animals for these purposes. Altogether, this has hindered the potential expansion of organoid applications in a number of field and applications.
AM: Can you tell us about QGel and what makes it unique?
CS: QGel is the only fully synthetic hydrogel adaptable to a multitude of cell types which supports the physiologically accurate 3D growth of cells. Small and large molecules, degradable linkers and stiffness properties can all be fine-tuned and altered to promote biologically accurate tissue growth. As a wide range of properties defining each gel can be tightly regulated, QGel technology ensures batch-to-batch consistency and scalability required for highly-reliable scientific quality. For the first time, the use of patient derived organoids is suitable for industrial applications, diagnostics and clinical development thanks to the QGel platform.
AM: What difference could QGel make to drug discovery and development?
CS: QGel is well-positioned to address the shortcomings of the current approach to drug discovery. Today, drug discovery programs must choose between highly physiologically relevant disease models which are not scalable for industrial applications (such as animal-derived gels), or highly scalable systems which have low physiological relevance (such as 2D monolayered platforms). QGel allows for high throughput screening with complex 3D assays using patient derived tissues – which means it will not take too long before organoids will start boosting the efficiency and success rate of industrial screening campaigns.
What is even more important for patient and healthcare systems in general, QGel’s technology has the ability to improve the patient journey for those millions affected by cancer. QGel diagnostic tools can test drug efficacy directly on tumour cells grown from biopsy, so that patients can receive therapies tailored specifically to their disease. By unlocking the full potential of patient-derived ‘organoids’ in diagnostics and medicine, QGel may finally open the gateway to personalized treatments for improving patient care.
Colin Sanctuary was speaking to Anna MacDonald, Editor for Technology Networks.