ArticleMolecular neurobiology2024
Neural Differentiation and spinal cord organoid generation from induced pluripotent stem cells (iPSCs) for ALS modelling and inflammatory screening.
Article in Molecular neurobiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 14 citations in OpenAlex.
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Stem cell derived neural organoid approaches for neurological diseases.Neural regeneration research · 2026Article
- Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.Nature reviews. Neuroscience · 2026Review
- Purpose-Adaptable Reinforced 3D Hyaluronic-Acid Based Platform to Study Pathomechanisms of the Central Nervous System.Advanced healthcare materials · 2026Article
- Development and characterization of 3D spinal cord organoids to advance the study of amyotrophic lateral sclerosis.Molecular biomedicine · 2026Article
- Artificial intelligence-driven nano-enhanced stem cell therapy for neurodegenerative diseases: from rational design to clinical translation.Journal of nanobiotechnology · 2026Review
- Review
- Organoid research: new concepts and new technologies.Burns & trauma · 2026Review
- Modeling ALS in a dish: how organoids are transforming research.Frontiers in medicine · 2026Review
- Generation of Neural Organoids and Their Application in Disease Modeling and Regenerative Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Review
- Toxicity assessment using neural organoids: innovative approaches and challenges.Toxicological research · 2025Review
- Review
- Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials.Brain sciences · 2025Review
- Patient-derived tumor organoids: A preclinical platform for personalized cancer therapy.Translational oncology · 2025Review
- Modeling neurodegenerative diseases with brain organoids: from development to disease applications.Frontiers in cell and developmental biology · 2025Review
- Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants.ACS chemical neuroscience · 2025Article
- Progress in spinal cord organoid research: advancing understanding of neural development, disease modelling, and regenerative medicine.Biomaterials translational · 2024Review
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
C9orf72 genetic mutation is the most common genetic cause of ALS/FTD accompanied by abnormal protein insufficiency. Induced pluripotent stem cell (iPSC)-derived two-dimensional (2D) and three-dimensional (3D) cultures are providing new approaches. Therefore, this study established neuronal cell types and generated spinal cord organoids (SCOs) derived from C9orf72 knockdown human iPSCs to model ALS disease and screen the unrevealed phenotype. Wild-type (WT) iPSC lines from three healthy donor fibroblasts were established, and pluripotency and differentiation ability were identified by RT-PCR, immunofluorescence and flow cytometry. After infection by the lentivirus with C9orf72-targeting shRNA, stable C9-knockdown iPSC colonies were selected and differentiated into astrocytes, motor neurons and SCOs. Finally, we analyzed the extracted RNA-seq data of human C9 mutant/knockout iPSC-derived motor neurons and astrocytes from the GEO database and the inflammatory regulation-related genes in function and pathways. The expression of inflammatory factors was measured by qRT-PCR. The results showed that both WT-iPSCs and edited C9-iPSCs maintained a similar ability to differentiate into the three germ layers, astrocytes and motor neurons, forming SCOs in a 3D culture system. The constructed C9-SCOs have features of spinal cord development and multiple neuronal cell types, including sensory neurons, motor neurons, and other neurons. Based on the bioinformatics analysis, proinflammatory factors were confirmed to be upregulated in C9-iPSC-derived 2D cells and 3D cultured SCOs. The above differentiated models exhibited low C9orf72 expression and the pathological characteristics of ALS, especially neuroinflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.