タイトル：

Let’s Get Connected: Building Networks with Brain Organoids

 

講演者：

Yoshiho Ikeuchi

Institute of Industrial Science, The University of Tokyo

 

要旨：

Brain organoids (neural organoids) derived from human pluripotent stem cells are artificial tissues that recapitulate structures and cell compositions of the human brain. Brain organoids are expected to play an important role in advancing our understanding of the brain and in developing new therapies. However, current brain organoids face several challenges. While early developmental stages can be reproduced, they remain immature and it is difficult to model the adult brain. Moreover, because neural organoids form spontaneously based solely on cellular properties, they reproduce only parts of the brain and cannot mimic the way many regions are interconnected in vivo.

  To address this, we are developing methods to assemble neural organoids into neural circuits by controlling axonal outgrowth within microdevices. In this approach, iPS cell–derived cerebral organoids are placed in small wells at the ends of narrow microchannels. Axons extending from each organoid grow through the channel and connect to the organoid on the opposite side, ultimately forming a reciprocally connected structure. The axon bundles linking the organoids can be regarded as mimicking nerve-fiber tracts such as the corpus callosum and subcortical axonal tracts. We refer to brain organoids connected via axonal bundles as “connectoids.”

  Connectoids exhibit more complex and vigorous activity than single organoids or assembloids. In connectoids, when action potentials in the inter-organoid axons are suppressed, synchrony between organoids is lost and the overall level of neural activity drops sharply. As these examples illustrate, a key advantage of constructing neural circuits in vitro is the ability to alter structure and patterns of axonal connectivity to interrogate resulting changes in neural activity.

  Another major challenge for brain organoids is the absence of continuous input signals from sensory organs. We are therefore also developing methods to induce functional changes in circuit architecture through sustained stimulation. Including these efforts, I would like to discuss the current state and future potential of brain organoid research.

 

Reference:

Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons.

Tatsuya Osaki, Tomoya Duenki, Siu Yu A. Chow, Yasuhiro Ikegami, Romain Beaubois, Timothée Levi, Nao Nakagawa-Tamagawa, Yoji Hirano, Yoshiho Ikeuchi Nature Communications 15 2945 2024