June 15, 2017 (Vol. 37, No. 12)
New Synthetic 3D Microenvironment Mimics Native Biology
For in vitro cellular assays, the extracellular matrix—the material between cells—often is overlooked, but changes within this microenvironment affect cells’ proliferation and differentiation and, ultimately, their biophysiology. That, in turn, affects how organoids develop, which significantly affects the accuracy of data derived from in vitro cellular models.
To enhance accuracy and reliability, and expand the types of tissues that may be grown into organoids, QGel has developed a range of synthetic extracellular 3D matrices, unique to each organ type. Each matrix is capable of mimicking key features of the native human tissue.
“The concept of cells organized into the organs in our body is well understood, but people often forget there’s something—a matrix material—between the cells that is as important as the cells themselves to make our organs function” Colin Sanctuary, Ph.D., CEO and co-founder of QGel, points out.
Until the past few years, labs and diagnostic centers have grown organoids in xenogel, a natural, animal-derived extracellular matrix. That xenogenic microenvironment, however, has an undefined composition, so it fails to provide scientists with such defined key characteristics as matrix stiffness. Xenogel’s value is limited, therefore, to only certain tissue types, and beset with lot-to-lot variability. Even so, the resulting organoids are a close representation of native tissue.
“The full potential of organoid technology has been limited because of the bottleneck caused by the use of poorly defined animal-derived gels,” Dr. Sanctuary explains. “That limitation—along with its unsuitability for being scaled—made organoids accessible only to certain labs and scientists. QGel’s fully defined synthetic gel solutions offer an alternative that could expand the potential of organoid applications.
QGel’s Synthetic Matrix
QGel develops 3D synthetic analogs of the extracellular microenvironments in which a variety of specific cell types, from cell lines to patient-derived tissue, grow. The resulting tissues, when used for drug screening and patient assays, yield results comparable to those of native human cells.
In explaining the role of the extracellular matrix, Dr. Sanctuary likens cells to individual computers that become more powerful when connected. In the body, the extracellular matrix allows the cells to communicate and, therefore, to induce certain cellular behaviors. “One can promote or inhibit disease progression by changing specific factors in the extracellular environment. The catch is that you need to be able to change the extracellular matrix, which is what makes QGel’s technology unique,” he points out.
The QGel matrix uses a modular synthetic hydrogel network to define important extracellular matrix parameters governing, for instance, intestinal stem cell expansion and other organoid formation, as explained in an article published in Nature (November 2016). “This synthetic extracellular matrix is a door-opener to a new horizon of applications,” Dr. Sanctuary adds. Dozens of factors can be considered and adjusted, depending on the organoid to be grown.
That ability to fine-tune the extracellular matrix enables organoids to be developed that weren’t feasible using existing xenogels. This is possible because QGel’s biological, biophysical, and biochemical characteristics are tunable, Dr. Sanctuary says.
“We can add growth factors or peptides to induce growth. We can design the matrix to produce gels with varying degrees of stiffness. We can change the properties of how the gel degrades when exposed to certain cell types.” Natural gels’ “what you see is what you get” environment may take these factors into account, he says, “but you just don’t know which of these factors are influencing the cells’ behavior.”
In addition to providing solutions for pharmaceutical companies for drug screening and drug development, QGel also is working with key cancer centers to apply organoid technology to patient diagnostics.
For example, he says, “Clinical studies have been designed using our gel as an integral component.” Many of those studies grew from research that incorporated a natural extracellular matrix but were cost prohibitive or could not be scaled up because of xenogels’ batch-to-batch variability. The QGel matrix overcomes that obstacle as well as the ethical or regulatory concerns of using rat-based xenogenic materials with patient material. Applications include target identification and validation, screening, lead optimization, patient stratification and, more ambitiously, companion diagnostics and personalized medicine.
In forming the company in 2009, “My approach focused on scalability and industrialization,” Dr. Sanctuary says. “Look at the number of cancer patients each year in the United States and Europe. The only way a technology like ours can have an effect is if it can be scaled.”
Dr. Sanctuary focused on two key scalability issues. The first was in manufacturing and the other was in usability.
The manufacturing issue was addressed by solving critical steps with the biochemistry of the gels to make them compatible with standard GMP machinery and quality standards. The company says it “can support any tissue, from cell lines to patient-derived tissue.” That entails attention to the details of gel compositions, reagents, and consumables, as well as to ensuring that sufficient quantities of gels reach the quality standards expressed by regulatory bodies and high-impact journals.
Then, to ensure usability, QGel translates its methodologies into protocols for automation that can be adopted easily by its partners. “Our goal is to provide our products and protocols so everyone (including non-Ph.D.s) can use them in their own labs,” Dr. Sanctuary emphasizes.
Product Expansion Planned
“We’re at the dawn of the industrialization of this technology,” Dr. Sanctuary says. QGel already has an extensive, rapidly growing, library of extracellular matrices formulations designed for specific cell types, including brain, breast, colon, kidney, lung, ovary, pancreas, placenta, prostate, and skin.
Expansion plans are based around developing a range of predictive cellular assays for a variety of cancer types for drug screening and discovery and, eventually, for personalized diagnostics.
The science has, to a large degree, been proven, says Dr. Sanctuary. The remaining milestone is commercial and is linked to the ability to industrialize.
“We have a novel product, and now, with powerful scientific evidence, we are starting to let people know about it,” he adds. “We are at the stage where we form close partnerships with research institutes that share our vision and with industrial clients so we can better understand and solve their problems with our technology. All our partnerships are based on solid scientific challenges that can’t be solved with standard technology.”
Location: Innovation Park, EPFL Building G, 1015 Lausanne, Switzerland
Phone: +41 21 694 0707
Principal: Colin Sanctuary, Ph.D., CEO and Cofounder
Number of Employees: 16
Focus: QGel designs synthetic 3D extracellular matrices capable of mimicking certain key features of native human tissue for in vitro drug screening and diagnostics.