The increasing complexity of novel therapies calls for disease models that take us closer than ever before to the in vivo situation, to maximize efficacy and safety evaluations of new experimental treatments. Significant improvements in our understanding of mammalian tissue development, homeostasis, and extracellular matrix biology, coupled with advances in human iPSCs (adult stem cells) and 3D culture have facilitated the generation of organoids and organ-on-a-chip technologies that serve as in vitro 3D models of healthy and diseased mammalian tissue. These technologies aim to become an integral part of research and drug discovery to provide novel insights into biological processes, mechanisms of disease, and responses to drug candidates and other treatments.
Tempo Bioscience attended the World Preclinical Congress Europe in Lisbon last month. This congress centers on preclinical research across a broad disease spectrum, and aims to illuminate the challenges and opportunities within early drug discovery and development. This years program covered topics spanning organ-on-a-chip, 3D cellular models, human induced pluripotent stem cells (hiPSC), and artificial intelligence and machine learning in drug discovery, to name a few. Of particular interest to Tempo Bioscience, the meeting highlighted progress as well as challenges with organs-on-chips, with the latter including scalability and adaption of the technology for applications in the biopharma industry. Here, we round up our top 3 symposium highlights within the organ-on-a-chip space.
- Integrating hiPSC-derived tissues in organ-on-a-chip systems
Peter Loskill PhD heads up the µOrgano-Lab at University of Tübingen, which merges hiPS cell technology and organoids with organ-on-a-chip concepts. The group incorporates hiPSC-derived tissues into microphysiological environments that recapitulate human genotypes, in vivo-like tissue structure, physiological functionality, and “vasculature-like” passage of bodily fluids, for example, blood.
Since hiPSCs are readily expandible, they can be used to generate material for high-throughput drug screening with disease-specific organ and tissue-models, and their pluripotency means that virtually any tissue or organ type is within reach, e.g., Retina-on-a-Chip or Heart-on-a-Chip. Besides representing patient/donor diversity and genotype/phenotype, organs-on-chips generated from hiPSCs remain viable for at least 1 month, allowing the experimental set-up to mature and further mimic the in vivo situation.
- Predicting Drug Responses with Lung-On-Chip Models
Olivier Guenat PhD runs the Organs-on-Chip Technologies group at the ARTORG Center, University of Bern. Through collaboration with clinical groups, his research combines engineering, tissue engineering and material sciences to generate a number of lung-on-chip models from primary patient cells that closely recapitulate the cellular environment of the lung parenchyma. These functional models mimic the lung alveolar barrier and the lung microvasculature, and serve as models to evaluate the effects of various compounds used for the treatment of respiratory diseases, for example, pulmonary fibrosis. His lab’s lung models consist of multiple cell type co-cultures: lung fibroblasts, pericytes, alveolar epithelial cells, and epithelial membrane endothelial cells. The main application in disease modeling is idiopathic pulmonary fibrosis.
- Microphysiological Systems – in vitro to in vivo Translation
Murat Cirit PhD is the Director of Biological Engineering at MIT. His work centers around the potential of human engineered microphysiological systems (MPS) – organs-on-chips and organoids – to examine and evaluate toxicity profiles of drug candidates before clinical trials; his work aims to reduce therapeutic attrition rates by providing more human-based in vitro assays for preclinical development than conventional in vitro and animal models. However, before the full potential of these technologies can be realized, robust ways to ensure in vitro-in vivo (MPS-to-human) translation are needed and many projects are underway to complete these evaluations. The budding area of quantitative systems pharmacology (QSP), which merges quantitative experimental biology, computational biology and biostatistics, may address that need by providing unbiased testing and validation of MPS technologies across research groups in academia and industry. The hope is that transparent and unbiased MPS testing will aid researchers and ensure well-characterized and independently validated MPS platforms for use in drug development and toxicology testing that government agencies may use in the regulatory decision-making process. QSP is in its infancy currently, but the long-term goal of its applications is to examine patient relevant drug induced toxicities and multi-organ toxicities at an early stage during drug development and to ultimately reduce therapeutic attrition rates.
At Tempo Bioscience, we strongly believe in the advantages of using human iPSC-derived models for target validation, early-stage drug discovery, preclinical development, and biomarker discovery. Our portfolio of genetically confirmed and multi-donor iPSC-based models serve to validate compound screening, target discovery, and preclinical biomarker development. The cell based models serve as “preclinical trials” to evaluate promising drug candidates. When utilized appropriately, this new process can improve the efficiency of pharmaceutical development.
Article by Karen O’Hanlon Cohrt PhD. Contact Karen at email@example.com.
Karen O’Hanlon Cohrt is a Science Writer with a PhD in biotechnology from Maynooth University, Ireland (2011). After her PhD, Karen moved to Denmark and held postdoctoral positions in mycology and later in human cell cycle regulation, before moving to the world of drug discovery. Her broad research background provides the technical know-how to support scientists in diverse areas, and this in combination with her passion for writing helps her to keep abreast of exciting research developments as they unfold. Follow Karen on Twitter @KarenOHCohrt. Karen has been a science writer since 2014; you can find her other work on her portfolio.