Establishment of an Organ-on-a-chip facility for Veterinary Species

Organs-on-chips (OoC) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic species physiology, the chips are designed to control cell microenvironments and maintain tissue-specific functions. Indeed, compared to traditional 2D cell culturing, such as primary cell cultures or tissue slices , organ-on-a-chip systems allow the controlled co-culture of different cells to mimic various structures and functions of tissues and organs, such as blood-brain barrier, lung and heart. More importantly, OoC reduce the sample volume substantially, reduce the cost of reagents and maximize information gleaned from precious samples by real time analysis, provide gains in scalability for screening applications and batch sample processing analogous to multi-well plates. OoC technology allows researchers to replicate the function of tissues and organs, bridging the gap between animals and human systems, but also reducing the need for large animal numbers, thus being in-line with the 3Rs. OoC are seen as an exciting in vitro alternative to assess new systems for regenerative system as well as vaccinology.
This proposal requests funding to purchase an Emulate Zoe device. This culture module provides dynamic culture conditions for up to 12 Organ-Chips. Users can set a range of automated flow and cyclic stretch parameters depending on study needs As an open platform, Zoë enables researchers to build a wide variety of organ models for myriad applications-from disease modeling, to target validation, to drug from disease modeling, to target validation, to drug candidate safety and efficacy evaluation.
Indeed, research carried out at the RVC and elsewhere has identified multiple possibilities to use such a system, in addition to classical primary cell cultures/tissue slices to assess the development of new vaccines/vaccine approaches by better understanding host-pathogen interaction in a 3d tissue complex, the development of regenerative medicine therapies (e.g. stem cell therapy for tendon, heart and eye), kidney failures and cancer in a multi-cell system, allowing for the interaction of tissue with other cell types/treatment strategies to be analysed.

Acquiring this Zoe Culture module would not only enable researchers to determine how target proteins implicated in these conditions perturb the cellular bioenergetic profile and how potential new therapies might restore cellular health.

Veterinary medicine is currently facing enormous global challenges. We must reduce pro-/ metaphylactic antimicrobial usage to prevent further rise in antimicrobial resistance and to reduce antimicrobial residues into the food chain and the environment, we must combat the north- and west-wards spread of infectious diseases due to global warming and identify ways to produce more protein for an ever-growing human population whilst maintaining high animal welfare standards. In addition, with pet ownership increasing and expectations of owners demanding treatments for degenerative chronic diseases of ageing, veterinary research needs to provide science-led personalised regenerative medicine solutions.
To support our expanding research in the area of vaccinology and regenerative medicine, we request funding for an Emulate Zoe Organ-on-ac-chip device, which provides a tissue-level read-out for use in cell-cell interaction, host-pathogen interaction and tissue repair. Specifically, we intend to use the device to assess:
Vaccinology: new control strategies to be developed for tuberculosis, bovine and porcine respiratory diseases complex and coccidiosis in chicken. All these diseases affect mucosal surfaces in the lung/gut, involve not only host-pathogen interaction but also immune cell/tissue interaction.
Regenerative Medicine: characterisation of the interaction of stem cells with host tissue (tendon, heart, eye) as well as immune cells of the recipient
Clinical settings: facets of neonatal brain injury , oxidative stress in propagating progressive kidney injury which is a fundamental process impacting on human and companion animal healthy ageing, and neuro-eondocrine tumors.
For a variety of these settings, the OoC approach would not only results in fewer target animals to be used (obeying 3R guidance), but veterinary species/settings are a more appropriate model for human medicine, thus enhancing OneHealth approaches.