NAMs and MPS and Organoids, Oh My!

By Breanne Kincaid | January 24, 2024

What’s in a name? When it comes to alternative models in animal testing, there are numerous terms and acronyms that can complicate the lay understanding of scientific efforts to develop human-relevant, non-animal toxicity testing strategies. Some terms are broad enough to encompass multiple technologies and can be used interchangeably in certain contexts, but not others. If you need a guide to these terms, keep reading – they are explained below.

NAM or NAMs (New Approach Methodology(s)): Regulators have adopted a broad perspective of what constitutes a new approach methodology owing to the fact that there is no single legal definition of the term. The US Environmental Protection Agency (EPA) defines NAMs as explicitly non-animal technologies, methodologies, or approaches used in the context of chemical hazard and risk assessment. The European Chemicals Agency (ECHA) specifies that any in silico, in chemico, or in vitro assays, as well as modern “omics” approaches such as genomics, proteomics, or metabolomics, can fall under the umbrella of a NAM. Thie ECHA definition includes approaches that use animals, but may use fewer animals. In both cases, the phrase emphasizes novel approaches that deviate from traditional animal toxicity testing.

MPS (Microphysiological System): A microphysiological system, or MPS, is a complex in vitro model in which cells are cultured to better replicate the structure and function of a tissue or organ. These cells are generally grown in an engineered system that mimics actual tissues or organs. MPS also frequently add physiological elements such as incorporating fluid flow to mimic circulation, mechanical movement, three dimensional structural elements, and co-culturing cell populations together. MPS is a broad term that includes more specific descriptions of in vitro systems such as spheroids, organoids, and organs on a chip. Each of these four (organoids, assembloids, spheroids, and organs-on-a-chip) would fall under the umbrella term of an MPS.

Organoid: Organoids are in vitro models that generally meet three requirements. They are self-organizing, include multiple cell types which mature together over weeks to months, and exhibit cytoarchitectural and functional features of the organ they model. They can be generated using three dimensional or a combination of two-dimensional and three-dimensional methods, and are often generated using pluripotent stem cells, or stem cells that can mature into a diverse population of cells that make up an organ or organ system. However, they can also be comprised of donor-derived tissue. Guided organoids are created when small molecular signals are used to guide organoid self-patterning towards a particular organoid region, while unguided organoids can display diverse organ-specific cell types not specific to a particular organ region.

Assembloid: An Assembloid, or an assembled organoid, is created by incorporating two separately generated organoids in order to enable functional modeling of two different organ regions. They are particularly common for modeling brain circuitry, and useful in studying midbrain-striatum assembloids to model Parkinson’s disease.

Spheroid: Spheroids represent a less complex three dimensional in vitro model than organoids. They are generated by combining separately generated cell types in three-dimensional culture, and as a result exhibit less extensive self-organization properties. Generally, the capacity for self-organization and early co-development of cell types are the primary differentiating factors between spheroids and organoids.

Organ-on-a-Chip: An organ-on-a-chip system is a microphysiological system cultured in a microfluidic chip that allows the delivery of culture medium and signaling factors through small microchannels. This allows specific patterning, such as the apical and basal polarity present in many lung on a chip models. As organ-on-a-chip technologies become more advanced, the field is generally aiming to move toward organ systems- and bodies-on-a-chip, allowing for the complex integration and fluid exchange between different body compartments.

In conclusion, the field of in vitro toxicology is moving forward rapidly, and there are numerous novel technologies now available that are poised to advance the physiological relevance of toxicity testing for human risk and hazard assessment. The major differences between these models include their complexity, their self-organization capacity, and the mode of delivery of test compounds, but all represent a promising shift to the 21st century of toxicology. 

The views expressed do not necessarily reflect the official policy or position of Johns Hopkins University or Johns Hopkins Bloomberg School of Public Health.