Figure 2

Exploring Environmental Neurotoxicity Assessment Using Human Stem Cell-Derived Models

Narimane Kebieche*, Farzana Liakath Ali, Seungae Yim, Mohamed Ali, Claude Lambert and Rachid Soulimani

Published: 15 November, 2024 | Volume 8 - Issue 1 | Pages: 054-068

jsctt-aid1044-g002

Figure 2:

Illustrates the use of 3D iPSC-based organoids and their applications in neurotoxicity research. (A.a) Cerebral organoids are derived from iPSC-generated embroids cultivated within spinning bioreactors during suspension culture. (A.b) Additionally, cerebral organoids are developed from iPSC-derived neural progenitor cells (NPCs) cultured within scaffold-assisted structures incorporating biomaterials like Matrigel. (A.c) Assembloids, formed by assembling cerebral organoids such as dorsal forebrain spheroids and ventral forebrain spheroids, enable the recreation of the dorsal-ventral forebrain axis, facilitating the investigation of interneuron migration. (A.d) The blood-brain-barrier model is generated from human iPSCs, producing astrocytes, pericytes, and endothelial cells that self-aggregate into neurospheres with defined structural layers. (A.e) Endogenous vascularization of cerebral organoids is induced by hETV2 infection to create vascular-like networks, enhancing organoid maturation. (A.f) A microfluidic organ-on-a-chip system models neural-vascular interactions with iPSC-derived neural progenitors and brain endothelial cells seeded in separate channels. (A.g) Multi-organ-on-a-chip systems enable simultaneous culture of hiPSC-derived cells (e.g., neural progenitors, hepatocytes, enterocytes) to replicate inter-organ interactions such as brain-liver-gut communication. (B.a) High-throughput screening of neurotoxic compounds is conducted using iPSC-derived models. (B.b) Mechanisms of toxicity, such as CPF-induced mitochondrial dysfunction and neurogenesis disruption, are elucidated. (B.c) Personalized medicine utilizes patient-specific iPSCs to create disease models for drug development, advancing candidates to clinical trials. (B.d) Inter-organ communication is modeled using multi-organ chips to assess the systemic effects of neurotoxic compounds through endpoints such as cell proliferation, differentiation markers, and metabolic activity. (Figure created with BioRender.com) 

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