Human induced pluripotent stem cells generated from epilepsy patients for use as in vitro models for drug screening

Hunter, Zoe; Leeson, Hannah C; Shaker, Mohammed R.; Wolvetang, Ernst; Vadlamudi, Lata

doi:10.1016/j.scr.2022.102673

Cited by 2 publications

(2 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, given the continuously growing global health care impact of aging-related diseases such as dementia, which are associated with an increase in senescent cell types in the brain that contributes to pathogenesis, the ability to identify and test compounds that can ameliorate brain aging are of enormous interest. Despite hPSCs being known to be epigenetically rejuvenated during the reprogramming process 20 , we find robust increases in senescent cells in cortical brain organoids cultured for prolonged periods of time. This is a promising development that now enables the screening of drugs that eliminate such senescent cells from the brain (senolytics) or that slow this process down (senostatics) 21 .…”

Section: Representative Resultscontrasting

confidence: 55%

Robust and Highly Reproducible Generation of Cortical Brain Organoids for Modelling Brain Neuronal Senescence In Vitro

Shaker

Hunter

Wolvetang

2022

JoVE

View full text Add to dashboard Cite

Brain organoids are three-dimensional models of the developing human brain and provide a compelling, cutting-edge platform for disease modeling and large-scale genomic and drug screening. Due to the self-organizing nature of cells in brain organoids and the growing range of available protocols for their generation, issues with heterogeneity and variability between organoids have been identified. In this protocol paper, we describe a robust and replicable protocol that largely overcomes these issues and generates cortical organoids from neuroectodermal progenitors within 1 month, and that can be maintained for more than 1 year. This highly reproducible protocol can be easily carried out in a standard tissue culture room and results in organoids with a rich diversity of cell types typically found in the developing human cortex. Despite their early developmental make-up, neurons and other human brain cell types will start to exhibit the typical signs of senescence in neuronal cells after prolonged in vitro culture, making them a valuable and useful platform for studying aging-related neuronal processes. This protocol also outlines a method for detecting such senescent cells in cortical brain organoids using senescence-associated betagalactosidase staining.

show abstract

Section: Representative Resultscontrasting

confidence: 55%