A Human Induced Pluripotent Stem Cell-Derived Tissue Model of a Cerebral Tract Connecting Two Cortical Regions

Kirihara, Takaaki; Luo, Zhangjie; Chow, Siu Yu A.; Misawa, Ryuji; Kawada, J.; Shibata, Shinsuke; Khoyratee, Farad; Vollette, Carole Anne; Volz, Valentine; Levi, Timothée; Fujii, Teruo; Ikeuchi, Yoshiho

doi:10.1016/j.isci.2019.03.012

Cited by 39 publications

(35 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This method can be applied to other types of neurons. Our group has shown capability to model a cerebral tract by using a modified method combined with cerebral organoid techniques 18 . Cortical spheroids were introduced into both compartments and the axons spontaneously elongated reciprocally toward each spheroid, and subsequently an axon bundle formed spontaneously.…”

Section: Representative Resultsmentioning

confidence: 99%

Three-Dimensional Motor Nerve Organoid Generation

Osaki

Chow

Nakanishi

et al. 2020

JoVE

Self Cite

View full text Add to dashboard Cite

A fascicle of axons is one of the major structural motifs observed in the nervous system. Disruption of axon fascicles could cause developmental and neurodegenerative diseases. Although numerous studies of axons have been conducted, our understanding of formation and dysfunction of axon fascicles is still limited due to the lack of robust three-dimensional in vitro models. Here, we describe a step-by-step protocol for the rapid generation of a motor nerve organoid (MNO) from human induced pluripotent stem (iPS) cells in a microfluidic-based tissue culture chip. First, fabrication of chips used for the method is described. From human iPS cells, a motor neuron spheroid (MNS) is formed. Next, the differentiated MNS is transferred into the chip. Thereafter, axons spontaneously grow out of the spheroid and assemble into a fascicle within a microchannel equipped in the chip, which generates an MNO tissue carrying a bundle of axons extended from the spheroid. For the downstream analysis, MNOs can be taken out of the chip to be fixed for morphological analyses or dissected for biochemical analyses, as well as calcium imaging and multi-electrode array recordings. MNOs generated with this protocol can facilitate drug testing and screening and can contribute to understanding of mechanisms underlying development and diseases of axon fascicles.

show abstract

Section: Representative Resultsmentioning

confidence: 99%

Three-Dimensional Motor Nerve Organoid Generation

Osaki

Chow

Nakanishi

et al. 2020

JoVE

Self Cite

View full text Add to dashboard Cite

show abstract

“…Like in the domains of interfacing and processing in the ANN, biological preparations have seen advances in the past years as well, with the advent of organoids such as those described in Kawada et al. (2017) , Kirihara et al. (2019) , and Lancaster and Knoblich (2014) featuring three-dimensional network morphologies.…”

Section: Discussionmentioning

confidence: 99%

Plasticity and Adaptation in Neuromorphic Biohybrid Systems

et al. 2020

Self Cite

View full text Add to dashboard Cite

Summary Neuromorphic systems take inspiration from the principles of biological information processing to form hardware platforms that enable the large-scale implementation of neural networks. The recent years have seen both advances in the theoretical aspects of spiking neural networks for their use in classification and control tasks and a progress in electrophysiological methods that is pushing the frontiers of intelligent neural interfacing and signal processing technologies. At the forefront of these new technologies, artificial and biological neural networks are tightly coupled, offering a novel “biohybrid” experimental framework for engineers and neurophysiologists. Indeed, biohybrid systems can constitute a new class of neuroprostheses opening important perspectives in the treatment of neurological disorders. Moreover, the use of biologically plausible learning rules allows forming an overall fault-tolerant system of co-developing subsystems. To identify opportunities and challenges in neuromorphic biohybrid systems, we discuss the field from the perspectives of neurobiology, computational neuroscience, and neuromorphic engineering.

show abstract

“…An 'organoids-on-a-chip' model of cerebral tracts has been generated by connecting two cerebral organoids via a bundle of axons that extends reciprocally in a 'handshake' manner, similar to that in developing brains 13 . In this model, a microfluidic compartment regulates the direction and assembly of growing axons, resulting in the formation of thick axon bundles that connect two cerebral organoids.…”

Section: Introductionmentioning

confidence: 99%

Advanced Complexity and Plasticity of Neural Activity in Reciprocally Connected Human Cerebral Organoids

Osaki

Ikeuchi

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Macroscopic axonal connections in the human brain distribute information and neuronal activity across the brain. Although this complexity previously hindered elucidation of functional connectivity mechanisms, brain organoid technologies have recently provided novel avenues to investigate human brain function by constructing small segments of the brain in vitro. Here, we describe the neural activity of human cerebral organoids reciprocally connected by a bundle of axons. Compared to conventional organoids, connected organoids produced significantly more intense and complex oscillatory activity. Optogenetic manipulations revealed that the connected organoids could re-play and recapitulate over time temporal patterns found in external stimuli, indicating that the connected organoids were able to form and retain temporal memories. Our findings suggest that connected organoids may serve as powerful tools for investigating the roles of macroscopic circuits in the human brain - allowing researchers to dissect cellular functions in three-dimensional in vitro nervous system models in unprecedented ways.

show abstract

A Human Induced Pluripotent Stem Cell-Derived Tissue Model of a Cerebral Tract Connecting Two Cortical Regions

Cited by 39 publications

References 24 publications

Three-Dimensional Motor Nerve Organoid Generation

Three-Dimensional Motor Nerve Organoid Generation

Plasticity and Adaptation in Neuromorphic Biohybrid Systems

Advanced Complexity and Plasticity of Neural Activity in Reciprocally Connected Human Cerebral Organoids

Contact Info

Product

Resources

About