Project description:Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix (BEM) to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with BEM significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.
Project description:<p>Lipids are critical for the structure, signaling, and metabolism of the central nervous system (CNS), yet their roles during human brain development remain underexplored due to limited tissue availability. X-linked adrenoleukodystrophy (ALD), a peroxisomal disorder caused by ABCD1 mutations, disrupts very long-chain fatty acid (VLCFA) degradation, leading to axonal degeneration and demyelination. To investigate lipid dynamics in CNS development and ALD pathogenesis, we generated human induced pluripotent stem cell (hiPSC)-derived cortical and spinal cord organoids and performed lipidomics over 200 days. Lipidomic analysis revealed a dynamic lipidome, with changes in lipid abundance, saturation, and chain length reflecting neurodevelopment. ALD hiPSC-derived organoids exhibited significant lipid alterations over time, including elevated VLCFA levels and reductions in brain-relevant lipids, such as sulfatides and gangliosides, in cortical organoids. These findings provide a foundational resource for studying lipid dynamics in CNS development and emphasize the value of organoids for understanding ALD and other CNS diseases.</p>
