Table 1 Summary of current ASD model classes with relevant advantages and disadvantages.
From: Human pluripotent stem cell (hPSC) and organoid models of autism: opportunities and limitations
Model | Application(s) | Advantage | Disadvantage |
|---|---|---|---|
Mouse models | In vitro, in vivo studies | Whole-body system capable of undergoing core developmental milestones shared between species | Failure to recapitulate species-specific cell types, gene expression, and developmental trajectories (ex: protracted maturation in humans) |
Postmortem tissues | Cellular characterizations | Directly sourced patient samples that were previously involved in a whole-body system | Samples subject to degradation, timepoints may be irrelevant to the pathology of interest |
Clinical imaging data (fMRI, MRI) | Imaging of whole-system in real time | Patient-specific data that can be performed longitudinally | Low resolution, and longitudinal studies often fail to sample a consistent population across time |
Clinical functional studies (EEG) | Recording of whole-system in real time | Patient-specific data that can be performed longitudinally | Low resolution, and longitudinal studies often fail to sample a consistent population across time |
Peripheric tissue (blood) | In vitro/molecular studies | Patient-specific data that can be drawn longitudinally | Data is generalizable and not neural-specific |
Human cell lines (SH-SY5Y, HEK239, etc.) | In vitro studies | Replicable, scalable model, amendable to CRISPR editing | Differentiation protocols fail to generate relevant cell types |
Behavioral studies | Human and mouse behavior phenotyping | Direct assessment of core ASD criteria (restricted interests, repetitive tasks) | Failure to address underlying pathology on a biological or molecular level |
Computational studies | In silico | Non-invasive, scalable | Requires training and use of datasets that are currently poorly understood |
Directed differentiation (2D) of iPSCs | In vitro modeling | Quick, scalable production of relevant cell types (NPCs, neurons) from patient source or isogenic background | Reductive, with exclusion of a 3D Cellular microenvironment |
Organoids | 3D in vitro modeling | Relevant, diverse cell types from patient source or isogenic background | Lack of vascularization, and a higher degree of heterogeneity |
