Abstract
For obvious reasons, such as, e.g., ethical concerns or sample accessibility, model systems are of highest importance to study the underlying molecular mechanisms of human maladies with the aim to develop innovative and effective therapeutic strategies. Since many years, animal models and highly proliferative transformed cell lines are successfully used for disease modelling, drug discovery, target validation, and preclinical testing. Still, species-specific differences regarding genetics and physiology and the limited suitability of immortalized cell lines to draw conclusions on normal human cells or specific cell types, are undeniable shortcomings. The progress in human pluripotent stem cell research now allows the growth of a virtually limitless supply of normal and DNA-edited human cells, which can be differentiated into various specific cell types. However, cells in the human body never fulfill their functions in mono-lineage isolation and diseases always develop in complex multicellular ecosystems. The recent advances in stem cell-based 3D organoid technologies allow a more accurate in vitro recapitulation of human pathologies. Embryoids are a specific type of such multicellular structures that do not only mimic a single organ or tissue, but the entire human conceptus or at least relevant components of it. Here we briefly describe the currently existing in vitro human embryo models and discuss their putative future relevance for disease modelling and drug discovery.
Highlights
For obvious reasons, such as, e.g., ethical concerns or sample accessibility, model systems are of highest importance to study the underlying molecular mechanisms of human maladies with the aim to develop innovative and effective therapeutic strategies
Animal models and immortalized traditional 2D human cell cultures were, and still are, indispensable and powerful enablers of the progress in biomedical research, it was obviously imperative to establish a new generation of multi-lineage platforms for accurate evaluations of the interactions between multiple human cell types in the context of diseases as well as for drug discovery
Such new models should allow the recapitulation of the three-dimensional (3D) multicellular ecosystem of human organs, tissues, and pathologies and should be amenable to genetic modifications, genomic screens, personalized medicine approaches, cancer studies, modeling of infections, microbiome studies, target identifications, high-throughput screenings, and preclinical pharmacokinetic and pharmacodynamic drug testing
Summary
It has always been a fundamental endeavor in biomedical research to improve the quality and efficiency of the experimental approaches to investigate human pathologies. The importance to investigate human brain cells to draw conclusions on the situation in men was recently supported by a single-cell RNA sequencing study describing extensive differences between homologous human and mouse cortex cell types, including marked alterations in proportions, laminar distributions, gene expression, and morphology [8] Another prominent example for limitations concerning cross-species comparisons is the mammalian embryogenesis. The time-consuming process of genetic and phenotypic adaption of such cells to culture conditions is rewarded by the establishment of a rapidly growing and cheap cellular model that is easy to handle and amenable to a variety of technological approaches These models exhibit clear limitations regarding their potential to mimic real in vivo human conditions including for example the interaction of cells of different origins [22,23]. The establishment of such models is still inefficient, their applicability for investigations of human pathologies is limited and high-throughput analyses are laborious and expensive [24,26,27,28]
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