Lena Smirnova, PhD is a research associate at the Johns Hopkins University Center for Alternatives to Animal Testing (CAAT), where she is director of the Systems Biology and Microphysiological systems program as well as the Center’s Education program. Dr. Smirnova earned her PhD in neuroscience Charité Universitätsmedizin Berlin, focusing on the role of microRNA in neural development, and pursued postdoctoral studies at the Federal institute for Risk Assessment in Berlin. Her scientific interests include developmental of organotypic brain cultures to study gene environmental interactions in neurodevelopmental disorders and neurodegeneration.
Dr. Smirnova will present work she is conducting with Dr. Thomas Hartung, a professor at Johns Hopkins Bloomberg School of Public Health and CAAT Director. In her talk, titled, “From microphysiological to micropathophysiological models”, she will discuss how organotypic cell culture of spheroids, organ- and human-on-chip technologies are a disruptive approach that increasingly enables the replacement of animal studies with healthy human tissues and their combinations. At the same time, the shortcomings of traditional animal tests, with respect to costs, duration, throughput and human relevance, are increasingly recognized. She will explore how major parts of (developmental) biology can now be recapitulated in vitro, especially in human stem-cell-derived models. In combination with computational approaches, acute and topical toxicities can be tackled, and an increasing number of animal-free OECD test guidelines is available. The real challenge, however, are the systemic toxicities (repeat-dose organ toxicities, reproductive toxicity and cancer) and drug development. We need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modeling these systems using bioengineering and virtual computer models (i.e., via systems biology or systems toxicology approaches). CAAT’s work on human iPSC-derived BrainSpheres will be used for illustration. Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities, i.e., the perturbation on organism level, without using substitute organisms (animals). The next challenge is to establish disease models, i.e., micropathophysiological systems (MPPS), to expand their utility to encompass biomedicine and especially drug development. Combining computational and experimental systems approaches and the challenges of validating them are discussed. The suggested 3S approach promises to leverage 21st century technology and systematic thinking to achieve a paradigm change in studying systemic effects.