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Organ-Chips Enhance the Maturation of Human iPSC-Derived Dopamine Neurons

ABSTRACT: Organ-Chips Enhance the Maturation of Human iPSC-Derived Dopamine Neurons

PROVIDER: PRJNA1001816 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25502054.fastq.gz	Fastqsanger.gz
	SRR25502055.fastq.gz	Fastqsanger.gz
	SRR25502056.fastq.gz	Fastqsanger.gz
	SRR25502057.fastq.gz	Fastqsanger.gz

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Organ-Chips Enhance the Maturation of Human iPSC-Derived Dopamine Neurons

Project description:While cells in the human body function in an environment where the blood supply constantly de-livers nutrients and removes waste, cells in conventional tissue culture well platforms are grown with a static pool of media above them and often lack maturity, limiting their utility to study cell biology in health and disease. In contrast, organ-chip microfluidic systems allow the growth of cells under constant flow, more akin to the in vivo situation. Here, we differentiated human induced pluripotent stem cells into dopamine neurons and assessed cellular properties in conventional multi-well cultures and organ-chips. We show that organ-chip cultures, compared to multi-well cultures, provide an overall greater proportion and homogeneity of dopaminergic neurons as well as increased levels of maturation markers. These organ-chips are an ideal platform to study mature dopamine neurons to better understand their biology in health and ultimately in neurological disorders.

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Project description:Organ-on-chip technology has accelerated in vitro preclinical research of the vascular system, and a key strength of this platform is its promise to impact personalized medicine by providing a primary human cell-culture environment where endothelial cells are directly biopsied from individual tissue or differentiated through stem cell biotechniques. But these methods are difficult to adopt in labs, and often result in impurity and heterogeneity of cells. This limits the power of organ-chips in making accurate physiological predictions. In this study, we report the use of blood-derived endothelial cells as alternatives to primary and iPSC-derived endothelial cells. Briefly, the genotype, phenotype and organ-chip functional characteristics of blood-derived outgrowth endothelial cells were compared against commercially available and most used primary endothelial cells and iPSC-derived endothelial cells. Through RNA sequencing we observe differences in gene expression profiles between different sources of endothelial cells, however blood-derived cells are relatively closer to primary cells than iPSC-derived suggesting that blood-derived endothelial cells may serve as an equally effective cell source for functional studies and organ-chips compared to primary cells or iPSC-derived cells.

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