Advantages and Potential Benefits of Using Organoids in Nanotoxicology

Abstract

Organoids are microtissues that recapitulate the complex structural organization and functions of tissues and organs. Nanoparticles have several specific properties that must be considered when replacing animal models with in vitro studies, such as the formation of a protein corona, accumulation, ability to overcome tissue barriers, and different severities of toxic effects in different cell types. An increase in the number of articles on toxicology research using organoid models is related to an increase in publications on organoids in general but is not related to toxicology-based publications. We demonstrate how the quantitative assessment of toxic changes in the structure of organoids and the state of their cell collections provide more valuable results for toxicological research and provide examples of research methods. The impact of the tested materials on organoids and their differences are also discussed. In conclusion, we highlight the main challenges, the solution of which will allow researchers to approach the replacement of in vivo research with in vitro research: biobanking and standardization of the structural characterization of organoids, and the development of effective screening imaging techniques for 3D organoid cell organization.

Human-Organoid-Based In Vitro Modeling for Environmental Toxicology

“…For instance, the benefits of coculture methods are evident in brain organoids, where coculturing with astrocytes and/or microglia during the early stages of neuron development supports neurogenesis and the maturation of neuronal cells . Neurons, astrocytes, and microglia form a crucial intercellular communication network as cells mature and diseases progress. − This interplay plays a pivotal role in human brain disorders, altering inflammatory signals and ultimately impacting the human brain microenvironment . Such a phenomenon is notably observed in neurodegenerative diseases, including Alzheimer’s disease.…”

“…Besides, conventional culture vessels used for organoid cultures lack the dynamic flow of cell culture media, resulting in the formation of a “necrotic core” within the organoids. ,, To address this issue, coculturing organoids with endothelial cell lines is employed as a common strategy to establish and enhance vascularization. − For example, a study by Shi et al. definitively established that vascularization of organoids significantly reduces the hypoxic environment in the core of the organoid .…”

Generating human skeletal myoblast spheroids for vascular myogenic tissue engineering

“…Moreover, due to the formation of endogenous extracellular matrix (ECM) and the increased expression of cadherins and integrins, aggregated cells are subjected to protection from external triggers, resulting in better cell viability rates and improved proliferation [21]. Next to that, spheroid cultures promote the expression of tissue-specific markers leading to a facilitated and accelerated differentiation and maturation process of the in vitro tissue [19,[21][22][23]. Also, spheroids possess the ability to fuse, which is essential to create larger tissues [24][25][26][27][28].…”

Novel Organoid Culture System for Improved Safety Assessment of Nanomaterials

“…12 Organoids, which are self-organized, multicellular 3D tissue, are considered promising models as an alternative to animal models. 8,13,14 Organoid models have some benefits in terms of having a comparatively longer lifespan than 2D cell models and being completely devoid of the ethical issues associated with animal testing. 15,16 In addition, organoids exhibit high similarity to their actual organ by having structural and functional properties of the organ.…”

“…Moreover, the Environmental Protection Agency (EPA) announced a plan to eliminate mammalian toxicity testing by 2035 . Organoids, which are self-organized, multicellular 3D tissue, are considered promising models as an alternative to animal models. ,, Organoid models have some benefits in terms of having a comparatively longer lifespan than 2D cell models and being completely devoid of the ethical issues associated with animal testing. , In addition, organoids exhibit high similarity to their actual organ by having structural and functional properties of the organ. , The significant cellular heterogeneity of organoids replicates the architectural barriers and complexity of real organs …”