4 Women Advancing Humane Science
Each year, IFER Graduate Fellowships are awarded to promising young scientists who are developing alternatives to use of animals in science. Meet 4 of the 2021-2022 recipients who have the potential to positively change the course of science by working to promote the advancement of humane and human-relevant methodologies that can spare animal suffering.
Katharina Kroll, Harvard University
“Development of a Perfusable Vascularized 3D-Kidney Organoid on a Chip for Nephrotoxicity Testing”
The goal of this project is to engineer a more complex in vitro model of the human kidney. Animal models often poorly predict the safety and effectiveness of drugs and can miss when the kidney is affected as a side effect of drugs. There are also limitations with existing cell-based kidney models, as they lack a blood supply (vasculature), do not include immune cells, and are often made of kidney cells that haven’t matured beyond early embryonic stages.
Katharina plans to address these limitations in her cell-based model. She will be building a kidney organoid-on-a-chip platform that integrates a functional vasculature network. She will also test whether this system can support the flow of blood cells delivered through this network. Then she will expose the kidney organoids to specific toxins and measure the effect of those treatments on the overall integrity and function of the organoids.
Ishita Virmani, Johns Hopkins University/Masaryk University
“3D Human iPSC-derived Brain Organoids as a Model for Developmental Neurotoxicity Assessment of Man-Made Chemicals”
This proposed project uses a brain organoid model derived from induced pluripotent stem cells, rather than commonly used animal models, to evaluate the developmental neurotoxicity potential of flame retardant chemicals. Ishita will expose the brain organoids, during the early stages of their development, to different flame retardants and will analyze the effect of those treatments using a number of different tests. Included among those tests will be assays regarding cell death, neurite outgrowth (a process in which developing neurons generate new projections as they grow), cell migration, gliogenesis (the generation of glial cells—cells that provide supporting function to the nervous system) and synaptogenesis (the formation of synapses between neurons in the nervous system).
Nuria Vilarnau, Karolinska Institute
“Mechanistic Analyses of Human Hepatocyte Plasticity”
This proposal aims to investigate regeneration of the human liver in vitro using a 3D sphere culture system. Chronic liver disease is becoming a major public health challenge, and the main therapeutic option for individuals suffering from end-stage liver disease is liver transplantation. However, another potential therapeutic approach could involve boosting the natural regenerative potential of liver cells.
While the main model to study tissue regeneration has relied on rodents, the translational impact of animal models is limited due to species differences. Traditional two-dimensional cell models of the human liver have also been inadequate to study this condition.
Nuria will be using a 3D cell culture system that enables the study of molecular and cellular biology of human adult liver regeneration. She will investigate the effects that small molecules and growth factors have on triggering human liver cells to grow and will perform a high-throughput gene expression study to better understand molecular mechanisms important for human liver cell growth.
Sarah Stuart, University of Melbourne
“Using brain tumor organoids to evaluate efficacy of novel inhibitors.”
Sarah’s project seeks to establish a large, patient-derived organoid collection to screen drugs to treat glioblastoma, an aggressive type of brain cancer. She will acquire resected glioblastoma tumors from surgeons at Royal Melbourne Hospital and will generate fifty organoid cultures over the course of her funding. She will screen seven new and FDA-approved drugs using these cell models and will then determine if the drugs inhibit critical signaling pathways in the organoids. Her project will enable the study of glioblastoma in a human-relevant way and has the potential to reduce reliance on glioblastoma animal models on a large scale, as the brain tumor organoids generated from her project will be shared with national and international collaborators.