Networked neural spheroid by neuro-bundle mimicking nervous system created by topology effect

Abstract

In most animals, the nervous system consists of the central nervous system (CNS) and the peripheral nervous system (PNS), the latter of which connects the CNS to all parts of the body. Damage and/or malfunction of the nervous system causes serious pathologies, including neurodegenerative disorders, spinal cord injury, and Alzheimer’s disease. Thus, not surprising, considerable research effort, both in vivo and in vitro, has been devoted to studying the nervous system and signal transmission through it. However, conventional in vitro cell culture systems do not enable control over diverse aspects of the neural microenvironment. Moreover, formation of certain nervous system growth patterns in vitro remains a challenge. In this study, we developed a deep hemispherical, microchannel-networked, concave array system and applied it to generate three-dimensional nerve-like neural bundles. The deep hemicylindrical channel network was easily fabricated by exploiting the meniscus induced by the surface tension of a liquid poly(dimethylsiloxane) (PDMS) prepolymer. Neurospheroids spontaneously aggregated in each deep concave microwell and were networked to neighboring spheroids through the deep hemicylindrical channel. Notably, two types of satellite spheroids also formed in deep hemispherical microchannels through self-aggregation and acted as an anchoring point to enhance formation of nerve-like networks with neighboring spheroids. During neural-network formation, neural progenitor cells successfully differentiated into glial and neuronal cells. These cells secreted laminin, forming an extracellular matrix around the host and satellite spheroids. Electrical stimuli were transmitted between networked neurospheroids in the resulting nerve-like neural bundle, as detected by imaging Ca2+ signals in responding cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-015-0109-y) contains supplementary material, which is available to authorized users.

Three‐Dimensional Models of the Human Brain Development and Diseases

“…[105] In another study, Jeong et al reported an improved model of neurospheroids cultured in PDMS microwells. [146] They used deep hemi-cylindrical channels well networked to enhance the formation of neurospheroids that release laminin and induce higher differentiation of the neural progenitor cells into glia and neurons. They also showed electrical activity likely due to the networks formed between the neurospheroids.…”

“…They also showed electrical activity likely due to the networks formed between the neurospheroids. [146] …”

Tissue engineered organoids for neural network modelling

“…Adding Aβ tot eh network resulted in decreased cell viability and neurite degeneration. A similar neurospehere network produced by Jeong et al 136 to study signal transmission through the CNSas a result of the partial breakdown in this system seen in Alzheimer's disease. Shallow (70µm) and deep (300µm) hemicylindrical channel networks between concave wells seeded with neural progenitor cells formed a self-aggregating network, Figure 2B.…”

“…Axonal signalling was recorded being transmitted between the spheroids, detected by Ca 2+ flux imaging. 136 Further models are summarised and reviewed in. 137,138 An important consideration when designing an in vitro model of the brain is interstitial fluid flow.…”

Translating advances in organ‐on‐a‐chip technology for supporting organs

“…Central nervous system (CNS) CNS axons, 63 neuronal networks, 22,23,28 cortical cell layers, 24 miro-bloodbrain barrier (BBB), 26 BBB (neurovascular unit) 25 neurovascular unit, 38 brain barriers (blood-brain, brain-CSF, and blood-CSF Blood brain barrier). 39…”