The problem that we addressed in this PoC project is that the pharmaceutical companies do not develop radically new drugs anymore, because the development process lasts ten years and costs around one billion euro. The process of regulatory approval has a 99.9% overall failure, of which 96.4% because the drug efficacy measured in vitro is almost never confirmed in animals. In fact, the most widespread technology used to test therapeutic agents in vitro, a flat culture dish in which single cell populations are cultured and the drug to be tested is added to the culture, is obsolete. In many pathologies such as cancer and neurodegeneration, in vivo response to drugs is based on complex interactions, occurring in three-dimensions (3D) between several cell populations, and by slowly-developing processes lasting well beyond the few hours of a standardised test in vitro. To solve this problem, in the context of an ERC consolidator grant (CoG) that I led, I integrated a novel micro-patterned 3D substrate for stem cell culture, called the “nichoid”, into an existing microfluidic optically accessible bioreactor (MOAB). The MOAB allows to culture 3D organoids of few millimetres in size, under continuous perfusion of the culture medium, infusion of the drug to be tested and diagnostics of cell response both in real time and also post-cultivation. Both the original inventions (the nichoid and the MOAB) are covered by granted patents that have originated in the frame of the CoG project (www.nichoid.polimi.it/erc-poc-moab).
The results obtained from this PoC project were: 1) confirmation of the technical feasibility of integrating the nichoid culture substrate in the MOAB. We characterized the fluid-dynamics of the bioreactor chamber modified to accommodate the nichoid substrate, both by computational modelling and by hydraulic testing; our results show that the MOAB-nichoid system represents an efficient system to culture cells in a 3D micro-environment in which the medium flow is uniformly distributed and the induced wall shear stress allows to reproduce the niche environment not only for the 3D spatial distribution but also for the fluid flow distribution; 2) confirmation of the commercial feasibility to move to the market the MOAB-nichoid. We set a market assessment and an actionable IPR strategy with identification of a suitable exploitation strategy for valorising the patent/know how. Most importantly, during this PoC we managed to acquire an investment of 80,000 Euro and we activated a university spin-off company, MOAB S.r.l. (www.moab-research.com) that has already acquired the license for both patents from the PoC hosting institution, employed one young biotechnologist at full time and started the commercialisation of the device; 3) I won a highly competitive research grant of 100,000 pounds from an English body, NC3Rs; the project was aimed at adapting the MOAB-nichoid to test in vitro the oncogenic potential of gene-edited hematopoietic stem cells, already used in human therapies to cure blood disorders. We managed to provide a proof-of-concept of this frontier application for the MOAB-nichoid and the company MOAB S.r.l. will now be the lead proponent of a Phase 2 grant of 1 million pounds.
