Size-controllable networked neurospheres as a 3D neuronal tissue model for Alzheimer's disease studies

Choi, Yoon Jung; Park, Ji Soo; Lee, Sang Hoon

doi:10.1016/j.biomaterials.2013.01.038

Cited by 91 publications

(100 citation statements)

References 29 publications

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“…This challenge may be circumvented by adapting the current protocol for controlling the size of cultured rodent prenatal neural aggregates 74. It will also be important to determine the clonal heterogeneity of neural aggregates and to determine how this heterogeneity differs between early and late passage NSC‐derived aggregates.…”

Section: Discussionmentioning

confidence: 99%

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

Clarkson

Patel

LaFrance‐Corey

et al. 2017

Ann Clin Transl Neurol

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ObjectiveInjury‐associated axon‐intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN γ) signals are known to induce expression of major histocompatibility class I (MHC I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen‐specific CD8+ T cells. We sought to determine whether the same is true in human neurons.MethodsA novel microisolation chamber design was used to physically isolate and manipulate axons from human skin fibroblast‐derived induced pluripotent stem cell (iPSC)‐derived neuron‐enriched neural aggregates. Fluorescent retrobeads were used to assess the fraction of neurons with projections to the distal chamber. Axons were treated with IFN γ for 72 h and expression of MHC class I and antigen presentation genes were evaluated by RT‐PCR and immunofluorescence.ResultsHuman iPSC‐derived neural stem cells maintained as 3D aggregate cultures in the cell body chamber of polymer microisolation chambers extended dense axonal projections into the fluidically isolated distal chamber. Treatment of these axons with IFN γ resulted in upregulation of MHC class I and antigen processing genes in the neuron cell bodies. IFN γ‐induced MHC class I molecules were also anterogradely transported into the distal axon.InterpretationThese results provide conclusive evidence that human axons are competent to express MHC class I molecules, suggesting that inflammatory factors enriched in demyelinated lesions may render axons vulnerable to attack by autoreactive CD8+ T cells in patients with MS. Future work will be aimed at identifying pathogenic anti‐axonal T cells in these patients.

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Section: Discussionmentioning

confidence: 99%

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

Clarkson

Patel

LaFrance‐Corey

et al. 2017

Ann Clin Transl Neurol

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“…Self-assembled aggregate cultures, which encompass spheroids, embryoid bodies, neurospheres, and microtissues, can be formed through suspension culture, in concave microwells, on sponge-gel matrices, and by a variety of other methods [12][13][14][15][16][17][18]. Neural spheroids can be produced using primary neural cells or neural cell lines such as the SK-N-SH neuroblastoma cell line for brain tumor studies [12,13].…”

Section: Methods For 3d Cell Culturementioning

confidence: 99%

“…Neural spheroids can be produced using primary neural cells or neural cell lines such as the SK-N-SH neuroblastoma cell line for brain tumor studies [12,13]. Neural stem cell aggregates can also be used, but these aggregates have been criticized for being very sensitive to cell culture conditions, resulting in inconsistently differentiated cells even between experimental trials [14,15]. In addition, all spheroids are limited by the size of the aggregate.…”

Section: Methods For 3d Cell Culturementioning

confidence: 99%

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Developments in 3D neural cell culture models: the future of neurotherapeutics testing?

Frampton

2016

Expert Review of Neurotherapeutics

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“…10 Historically, 3D neural cultures were developed using scaffolds, 3,[11][12][13][14] and complex cell compartmentalization and organization have been achieved through scaffold design. [15][16][17] Recently, neural cells have been cultured through self-assembly into spheroid structures in which they can produce their own matrix; 18,19 these spheroids have been suggested to approximate in vivo-like cell behavior better than scaffold-based cultures. 20,21 Several studies of the nervous system function or disease have incorporated high levels of technological requirements in their cell cultures.…”

mentioning

confidence: 99%

Three-Dimensional Neural Spheroid Culture: AnIn VitroModel for Cortical Studies

Dingle

Boutin

Chirila

et al. 2015

Tissue Engineering Part C: Methods

119

117

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There is a high demand for in vitro models of the central nervous system (CNS) to study neurological disorders, injuries, toxicity, and drug efficacy. Three-dimensional (3D) in vitro models can bridge the gap between traditional two-dimensional culture and animal models because they present an in vivo-like microenvironment in a tailorable experimental platform. Within the expanding variety of sophisticated 3D cultures, scaffold-free, self-assembled spheroid culture avoids the introduction of foreign materials and preserves the native cell populations and extracellular matrix types. In this study, we generated 3D spheroids with primary postnatal rat cortical cells using an accessible, size-controlled, reproducible, and cost-effective method. Neurons and glia formed laminin-containing 3D networks within the spheroids. The neurons were electrically active and formed circuitry through both excitatory and inhibitory synapses. The mechanical properties of the spheroids were in the range of brain tissue. These in vivo-like features of 3D cortical spheroids provide the potential for relevant and translatable investigations of the CNS in vitro.

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Size-controllable networked neurospheres as a 3D neuronal tissue model for Alzheimer's disease studies

Cited by 91 publications

References 29 publications

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

Retrograde interferon‐gamma signaling induces major histocompatibility class I expression in human‐induced pluripotent stem cell‐derived neurons

Developments in 3D neural cell culture models: the future of neurotherapeutics testing?

Three-Dimensional Neural Spheroid Culture: AnIn VitroModel for Cortical Studies

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