Concise Review: Induced Pluripotent Stem Cell Models for Neuropsychiatric Diseases

Abstract

The major neuropsychiatric conditions of schizophrenia, affective disorders, and infantile autism are characterized by chronic symptoms of episodic, stable, or progressive nature that result in significant morbidity. Symptomatic treatments are the mainstay but do not resolve the underlying disease processes, which are themselves poorly understood. The prototype psychotropic drugs are of variable efficacy, with therapeutic mechanisms of action that are still uncertain. Thus, neuropsychiatric disorders are ripe for new technologies and approaches with the potential to revolutionize mechanistic understanding and drive the development of novel targeted treatments. The advent of methods to produce patient‐derived stem cell models and three‐dimensional organoids with the capacity to differentiate into neurons and the various neuronal cellular lineages mark such an advance. We discuss numerous techniques involved, their applications, and areas that require further optimization. Stem Cells Translational Medicine 2017;6:2062–2070

Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells

“…Cerebral organoids, together with the recently developed assembloids, are three-dimensional in vitro structures that show great potential for investigating complex human genetic states and modeling aspects of human neurodevelopmental pathologies ( Quadrato and Arlotta, 2017 ; Chiaradia and Lancaster, 2020 ; Sidhaye and Knoblich, 2021 ). Organoid models of human MCDs can be generated either by introducing the disease-causing mutations into otherwise wild type IPSCs or by directly using patient-derived IPSCs ( Adegbola et al, 2017 ; Iefremova et al, 2017 ; Li et al, 2017 ; Fiddes et al, 2018 ; Klaus et al, 2019 ; Lopez-Tobon et al, 2019 ; Dhaliwal et al, 2021 ; Kyrousi et al, 2021 ; Wegscheid et al, 2021 ), with the latter being instrumental in personalized medicine. Among the animal models, macaques are particularly interesting as they recapitulate many of the cell biological features of human BPs ( Betizeau et al, 2013 ).…”

CIRM tools and technologies: Breaking bottlenecks to the development of stem cell therapies

“…Taken together, these early observations suggest that hiPSC can be used to model a polygenic disorder and potentially to identify patient specific treatments. This line of inquiry is continuing to contribute to our understanding of disease 16,17 …”

Blood-Based miRNA Biomarkers as Correlates of Brain-Based miRNA Expression

“…And more importantly, they are not designed to differentiate causal miRNA expression signatures from those that result from progression of the disease or from death. And lastly, the recent advent of methods to derive neuronal cells and brain organoids from pluripotent stem cells [reviewed in Adegbola et al (2017) and McKinney (2017) ] allows the investigation of patient samples that are representative of brain tissue; but development and characterization of these models are cost-prohibitive on a large scale and their relation to brain tissue sources, especially with respect to miRNA expression networks, is not yet well defined.…”