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Organoid research on human early development and beyond.

ABSTRACT: The organoid field has been developing rapidly during the last decade. Organoids for human pre-, peri- and post-implantation development have opened an avenue to study these biological processes in vitro, which have been hampered by lack of accessible research models for long term. The technologies of four fields, single cell omics sequencing, genome editing and lineage tracing, microfluidics and tissue engineering, have fueled the rapid development of the organoid field. In this review, we will discuss the organoid research on human early development as well as future directions of the organoid field combining with other powerful technologies.

SUBMITTER: Wen L

PROVIDER: S-EPMC10471100 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Organoid research on human early development and beyond.

Wen Lu L Tang Fuchou F

Medical review (2021) 20221031 5

The organoid field has been developing rapidly during the last decade. Organoids for human pre-, peri- and post-implantation development have opened an avenue to study these biological processes <i>in vitro</i>, which have been hampered by lack of accessible research models for long term. The technologies of four fields, single cell omics sequencing, genome editing and lineage tracing, microfluidics and tissue engineering, have fueled the rapid development of the organoid field. In this review, ...[more]

PMID: 37724162

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Project description:JOURNAL/nrgr/04.03/01300535-202501000-00032/figure1/v/2024-05-14T021156Z/r/image-tiff Human brain development is a complex process, and animal models often have significant limitations. To address this, researchers have developed pluripotent stem cell-derived three-dimensional structures, known as brain-like organoids, to more accurately model early human brain development and disease. To enable more consistent and intuitive reproduction of early brain development, in this study, we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture. This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation, resulting in a new type of human brain organoid system. This cerebral organoid system replicated the temporospatial characteristics of early human brain development, including neuroepithelium derivation, neural progenitor cell production and maintenance, neuron differentiation and migration, and cortical layer patterning and formation, providing more consistent and reproducible organoids for developmental modeling and toxicology testing. As a proof of concept, we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins. Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns, including bursts of cortical cell death and premature differentiation. Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity, accompanied by compensatory cell proliferation at ectopic locations. The convenience, flexibility, and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental, neurological, and neurotoxicological studies.

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Organoid research on human early development and beyond.

Publications

Organoid research on human early development and beyond.

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