Human stem cell-based disease modeling: prospects and challenges

Assessment of food toxicology

“…Recently, stem cell-based assays are being discussed as source for various toxicological applications [6,[55][56][57] thanks to the Nobel Prize-winning discovery of how to reprogram ordinary somatic cells to behave like embryonic stem cells [139]. Human-induced pluripotent stem cells (iPSCs) allow assays to consider an individual's genetic background and potential epigenetic influences that affect the variability of the toxicity response [56].…”

“…Stem cellbased models are also of particular interest for toxicity measurements which either lack extrapolability in rodent models such as for genotoxicity, cardiotoxicity, respiratory toxicity or for different stages of disorders which largely remain unknown such as neurological disorders (depression, anxiety, Alzheimer's and Parkinson's disease), autoimmune diseases (multiple sclerosis, type I diabetes, asthma), systemic infection, cancer and others[8,27,[58][59][60]. Although in early development, human stem cell models may further reduce the usage of animals in safety and risk assessment studies and offer the potential to dramatically enhance our understanding and thus prediction of the molecular basis of toxicity[6,[55][56][57].…”

“…The deeper understanding of the molecular mode of action on key targets of biological pathways have enhanced the predictivity and robustness of in vitro cell-based toxicity models and thus led to the improvement of food safety. Moreover, although in early development, stem cell-based screening or three-dimensional organotypic models will further increase the predictivity of acute toxicity and help to answer fundamental biological questions and/or enable testing of novel therapeutic approaches [6,7,[53][54][55][56][57].…”

“…By the use of comprehensive profiling via genomics, proteomics, transcriptomics, and metabolomics stem cell in vitro models offer an unprecedented opportunity to test the effects of potential food toxicants in a very predictive and personalized manner[6,[55][56][57]. Stem cellbased models are also of particular interest for toxicity measurements which either lack extrapolability in rodent models such as for genotoxicity, cardiotoxicity, respiratory toxicity or for different stages of disorders which largely remain unknown such as neurological disorders (depression, anxiety, Alzheimer's and Parkinson's disease), autoimmune diseases (multiple sclerosis, type I diabetes, asthma), systemic infection, cancer and others[8,27,[58][59][60].…”

Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems

“…In contrast to traditional twodimensional monolayer cell culture, which are often made of a single transformed cell type, organoids possess multiple cell types along with structural and cellular organization, and can possess multiple tissue layers such as an epithelium and mesenchyme. [4,[8][9][10][11][12] Organoids can be seen as bridging the gap between cell lines, and organotypic explant cultures (such as whole-organ or slice cultures), which have the cellular and structural complexity of the native tissue, but which are typically short-lived in culture. [13] Organoid cultures are appealing due to their ability to survive for long periods of time in vitro, for their cellular heterogeneity, and for their architecture and cellular organization that recapitulate some aspects of the native tissue.…”