Bio-printed, cryopreserved, 3D cell models to benefit drug discovery ANAPRINT’s pre-assembled cell technology offers industry flexibility, long-term storage options, and the uncoupling of cell-model assembly from analytical use; without compromising on predictive preclinical accuracy. Digital Economy Health © Sebastian Kaulitzki, Shutterstock Industry uses human cell models to study the biological effects of potential new treatments for human diseases. This has typically been done with aged cell lines, which has been found to compromise the tests’ predictive value. In clinical settings, the majority of candidate drugs selected this way failed, often after significant financial investment. For this cell-based analysis technique to be efficacious, industry now recognises that the cells must be able to ‘remember’ the tissue from whence they came. So-called ‘primary’ cells work best for this, especially when placed in a 3D environment, similar to that of their tissue of origin. However, making such 3D cell models has proven to be a technically-challenging process. AvantiCell Science’s solution, developed under the ANAPRINT project, was to use bio-printing of primary cells to create 3D cell models. This bio-printing technique was developed to place precise numbers of cells, along with the extracellular ‘glue’ which binds them together inside their tissue of origin, into every well of a culture plate. Industry typically uses plates containing 96 (12 x 8) wells or 384 (24 x 6) wells for rapid preclinical testing of drug candidates. “This bio-printing precision, its cell-friendliness, and the ability to assemble and position cellular micro-tissues consistently in every culture well, creates the ideal conditions in which to build a screening platform for drug discovery,” says Dr Colin Wilde, project coordinator. ‘Plug and Play’ The ANAPRINT team also discovered that the 3D cell models could be frozen in their culture wells, and then thawed and brought back to culture successfully. This combination of a pre-assembled 3D cell model, along with long-term cryopreserved storage options, offers customers much more efficient resource management, increasing the technology’s attractiveness for industry-wide adoption. It also delivered ANAPRINT’s goal of a scalable manufacturing process enabling production, banking and supply on demand, of 3D cell-based analysis products. Success was underlined by the team’s ability to bio-print liver cells and cell aggregates consistently, and to perform industry-standard toxicity tests using these 3D cell models. Positive-disruptive impact ANAPRINT contributes to efforts to replace animal experimentation with human cell-based analysis, addressing ethical and sustainability concerns. Additionally, expanded applications could accommodate otherwise-discarded biological materials (e.g. immune cells in blood transfusion extracts). Regarding industries based on life science, “By building preclinical tools which are more predictive of clinical behaviour, the failure of two-in-every-three, late stage development candidate drugs, should be reduced,” says Dr Wilde. “Hopefully this will lead to a reduction in the cost of developing new drugs, and the cost to healthcare systems of providing essential medication.” A 2D demonstrator was released to show-case the Cryotix™ cryopreservation technology, with the launch of the mature product expected within months of the project’s end. The first sales have already been secured to industry researchers and, post-project, the technology is expected to constitute a significant share of AvantiCell Science’s income within two years through both licensing and contracted application arrangements. The next, immediate steps will be to apply these technologies more widely to cells relevant to major human diseases. ANAPRINT’s technique is also of interest to other industry sectors, such as foods, nutraceuticals, complementary medicines and medical device materials. Applications in the field of nanomedicine and environmental nanotoxicity testing are also under consideration as potential markets. Keywords ANAPRINT, additive manufacturing, bio-printing, cell models, 3D, drug, pharmaceutical, cryopreservation, freeze, tissue, clinical
