Cerebral Organoids Maintain the Expression of Neural Stem Cell-Associated Glycoepitopes and Extracellular Matrix

Roll, Lars; Lessmann, Katrin; Brüstle, Oliver; Faissner, Andréas

doi:10.3390/cells11050760

Cited by 10 publications

(11 citation statements)

References 69 publications

(77 reference statements)

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“…4 ). Moreover, the co-localization of nestin and intermediate progenitor cell marker, (T-box brain protein 2) TBR2 indicate that the cerebral organoids possessed well-defined progenitor zone organization and neural identity 58 for all dynamic systems at day 120 but mostly in µ-platform and RCCS (Fig. 4a–c , Supplementary Fig.…”

Section: Resultsmentioning

confidence: 97%

Spatio-temporal dynamics enhance cellular diversity, neuronal function and further maturation of human cerebral organoids

et al. 2023

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The bioengineerined and whole matured human brain organoids stand as highly valuable three-dimensional in vitro brain-mimetic models to recapitulate in vivo brain development, neurodevelopmental and neurodegenerative diseases. Various instructive signals affecting multiple biological processes including morphogenesis, developmental stages, cell fate transitions, cell migration, stem cell function and immune responses have been employed for generation of physiologically functional cerebral organoids. However, the current approaches for maturation require improvement for highly harvestable and functional cerebral organoids with reduced batch-to-batch variabilities. Here, we demonstrate two different engineering approaches, the rotating cell culture system (RCCS) microgravity bioreactor and a newly designed microfluidic platform (µ-platform) to improve harvestability, reproducibility and the survival of high-quality cerebral organoids and compare with those of traditional spinner and shaker systems. RCCS and µ-platform organoids have reached ideal sizes, approximately 95% harvestability, prolonged culture time with Ki-67 + /CD31 + /β-catenin+ proliferative, adhesive and endothelial-like cells and exhibited enriched cellular diversity (abundant neural/glial/ endothelial cell population), structural brain morphogenesis, further functional neuronal identities (glutamate secreting glutamatergic, GABAergic and hippocampal neurons) and synaptogenesis (presynaptic-postsynaptic interaction) during whole human brain development. Both organoids expressed CD11b + /IBA1 + microglia and MBP + /OLIG2 + oligodendrocytes at high levels as of day 60. RCCS and µ-platform organoids showing high levels of physiological fidelity a high level of physiological fidelity can serve as functional preclinical models to test new therapeutic regimens for neurological diseases and benefit from multiplexing.

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Section: Resultsmentioning

confidence: 97%

Spatio-temporal dynamics enhance cellular diversity, neuronal function and further maturation of human cerebral organoids

et al. 2023

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“…Contrary to its function in these processes, its role in NPSCs is less known. Several studies have reported that CSPG is required for maintaining a stemness state in NPSCs in the SVZ, and have suggested that this activity is mediated by interaction with FGF-2 to promote cell proliferation (Bian et al, 2011;Roll et al, 2022;Sirko et al, 2010a). In spinal cord NSPCs, such FGF-2 activity was recently found to depend on the sulfation patterns of the CSPG-GAG chains that operate as docking sites for specific proteins (Schaberg et al, 2021).…”

Section: The Role Of Csps In the Hbsmentioning

confidence: 99%

Hindbrain boundaries as niches of neural progenitor/stem cells regulated by the extracellular matrix proteoglycan chondroitin sulphate

Hutchings

Nuriel

Lazar

et al. 2023

Preprint

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The interplay between neural progenitor/stem cells (NPSC) and their extracellular matrix (ECM), is a crucial regulatory mechanism that determines their behavior. Nonetheless, how the ECM dictates internal processes remains elusive. The hindbrain is valuable to examine this relationship, as cells in the hindbrain boundaries (HB), which arise between any two neighboring rhombomeres, express the NPSC-marker Sox2 while being surrounded with the ECM molecule chondroitin sulphate proteoglycan (CSPG), in chick and mouse embryos. CSPG expression was used to isolate HB/Sox2+ cells for RNA-sequencing, revealing their distinguished molecular properties as typical NPSCs, which express known and newly-identified genes relating to stem cells, cancer, matrisome and cell-cycle. In contrast, the CSPG-/non-HB cells, displayed clear neural-differentiation transcriptome. To address whether CSPG is significant for hindbrain development, its expression was manipulated in vivo and in vitro. CSPG-manipulations shifted the stem versus differentiation state of HB cells, evident by their behavior and altered gene expression. These results provide novel understanding on the uniqueness of hindbrain boundaries as repetitive pools of NPSCs in-between the rapidly-growing rhombomeres, which rely on their microenvironment to maintain undifferentiated during development.

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“…b) This schematic illustrates the temporal changes in the neural stem cell-associated glycoepitopes and ECM molecules present in human cerebral organoids. Reproduced with permission [81]. Copyright 2022, MDPI.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Small Joint Organoids 3D Bioprinting: Construction Strategy and Application

Zhang,

Li,

Wang

et al. 2023

Small

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Osteoarthritis (OA) is a chronic disease that causes pain and disability in adults, affecting ≈300 million people worldwide. It is caused by damage to cartilage, including cellular inflammation and destruction of the extracellular matrix (ECM), leading to limited self‐repairing ability due to the lack of blood vessels and nerves in the cartilage tissue. Organoid technology has emerged as a promising approach for cartilage repair, but constructing joint organoids with their complex structures and special mechanisms is still challenging. To overcome these boundaries, 3D bioprinting technology allows for the precise design of physiologically relevant joint organoids, including shape, structure, mechanical properties, cellular arrangement, and biological cues to mimic natural joint tissue. In this review, the authors will introduce the biological structure of joint tissues, summarize key procedures in 3D bioprinting for cartilage repair, and propose strategies for constructing joint organoids using 3D bioprinting. The authors also discuss the challenges of using joint organoids’ approaches and perspectives on their future applications, opening opportunities to model joint tissues and response to joint disease treatment.

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Cerebral Organoids Maintain the Expression of Neural Stem Cell-Associated Glycoepitopes and Extracellular Matrix

Cited by 10 publications

References 69 publications

Spatio-temporal dynamics enhance cellular diversity, neuronal function and further maturation of human cerebral organoids

Spatio-temporal dynamics enhance cellular diversity, neuronal function and further maturation of human cerebral organoids

Hindbrain boundaries as niches of neural progenitor/stem cells regulated by the extracellular matrix proteoglycan chondroitin sulphate

Small Joint Organoids 3D Bioprinting: Construction Strategy and Application

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