Leveraging the zebrafish to model organ transplantation

Abstract

Purpose of review The availability of organs for transplant fails to meet the demand and this shortage is growing worse every year. As the cost of not getting a suitable donor organ can mean death for patients, new tools and approaches that allows us to make advances in transplantation faster and provide a different vantage point are required. To address this need, we introduce the concept of using the zebrafish (Danio rerio) as a new model system in organ transplantation. The zebrafish community offers decades of research experience in disease modeling and a rich toolbox of approaches for interrogating complex pathological states. We provide examples of how already existing zebrafish assays/tools from cancer, regenerative medicine, immunology, and others, could be leveraged to fuel new discoveries in pursuit of solving the organ shortage. Recent findings Important innovations have enabled several types of transplants to be successfully performed in zebrafish, including stem cells, tumors, parenchymal cells, and even a partial heart transplant. These innovations have been performed against a backdrop of an expansive and impressive list of tools designed to uncover the biology of complex systems that include a wide array of fluorescent transgenic fish that label specific cell types and mutant lines that are transparent, immune-deficient. Allogeneic transplants can also be accomplished using immune suppressed and syngeneic fish. Each of these innovations within the zebrafish community would provide several helpful tools that could be applied to transplant research. Summary We highlight some examples of existing tools and assays developed in the zebrafish community that could be leveraged to overcome barriers in organ transplantation, including ischemia–reperfusion, short preservation durations, regeneration of marginal grafts, and acute and chronic rejection.

Zebrafish as a New Tool in Heart Preservation Research

“…Nonetheless, provided research is conducted with careful consideration of these limitations and used strategically in combination with more established models in experimental heart transplantation, zebrafish may serve to bridge a critical gap in heart preservation research. In another review, we discuss more broadly the zebrafish approach for organ transplantation research [ 59 ], while here we focus exclusively on heart preservation research.…”

Animal Models in Allogenic Solid Organ Transplantation

“…The discrepancy in this number is showing that there is still a tremendous need for research in this field. New approaches must be established to overcome the shortage of organs such as evaluation of marginal or organs of older donors to include them into the donor pool, improving organ protection strategies, and minimizing the ischemic and reperfusion damage or ex vivo machine perfusion for organ reconditioning [2,7].…”

“…Animal models are in need when in vitro or in silico systems cannot provide a reasonable and reproducible approach of an organism in vivo. The use of discarded human grafts to replace animal models is not feasible, as they are difficult to get and not available in a sufficient number to perform controlled studies [7].…”

“…In transplantation, the tight dependency between physiological functions, systemic interactions, and immune responses associated with the entire living system determine cell, tissue, or organ graft survival [7,8]. Therefore, animal models are essential to evaluate the therapeutic efficacy and safety of new approaches in the field of organ transplantation.…”

“…However, finding the right animal model can be challenging: small animal models require specifically skilled personnel with specialized microsurgery abilities, which is often not available. In addition to the ethical concerns and regulatory burdens, large animal studies are extremely labor-intensive and expensive [7,9].…”