title: A neurospheroid network-stamping method for neural transplantation to the brain.
abstract: Neural transplantation therapy using neural stem cells has received as potential treatments for neurodegenerative diseases. Indeed, this therapy is thought to be effective for replacement of degenerating neurons in restricted anatomical region. However, because injected neural stem cells integrate randomly into the host neural network, another approach is needed to establish a neural pathway between selective areas of the brain or treat widespread degeneration across multiple brain regions. One of the promising approaches might be a therapy using pre-made neural network in vitro by the tissue engineering technique. In this study, we engineered a three-dimensional (3D) tissue with a neuronal network that can be easily manipulated and transplanted onto the host brain tissue in vivo. A polydimethylsiloxane microchamber array facilitated the formation of multiple neurospheroids, which in turn interconnected via neuronal processes to form a centimeter-sized neurospheroid network (NSN). The NSN was transferable onto the cortical surface of the brain without damage of the neuronal network. After transfer onto the cortical tissue, the NSN showed neural activity for more than 8 days. Moreover, neurons of the transplanted NSN extended their axons into the host cortical tissue and established synaptic connections with host neurons. Our findings suggest that this method could lay the foundation for treating severe degenerative brain disease.
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Kato-Negishi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Onoe
authors.forename: Shoji
authors.initials: S
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004129:Dimethylpolysiloxanes / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000637:transplantation*; D011094:Polyethyleneimine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D004129:Dimethylpolysiloxanes; D011094:Polyethyleneimine