Human Cerebrospinal Fluid Promotes Neuronal Circuit Maturation of Human Induced Pluripotent Stem Cell-Derived 3D Neural Aggregates.

Stem Cell Reports
Julia IzsakSebastian Illes

Abstract

Human induced pluripotent stem cell (hiPSC)-derived in vitro neural and organoid models resemble fetal, rather than adult brain properties, indicating that currently applied cultivation media and supplements are insufficient to achieve neural maturation beyond the fetal stage. In vivo, cerebrospinal fluid molecules are regulating the transition of the immature fetal human brain into a mature adult brain. By culturing hiPSC-3D neural aggregates in human cerebrospinal fluid (hCSF) obtained from healthy adult individuals, we demonstrate that hCSF rapidly triggers neurogenesis, gliogenesis, synapse formation, neurite outgrowth, suppresses proliferation of residing neural stem cells, and results in the formation of synchronously active neuronal circuits in vitro within 3 days. Thus, a physiologically relevant and adult brain-like milieu triggers maturation of hiPSC-3D neural aggregates into highly functional neuronal circuits in vitro. The approach presented here opens a new avenue to identify novel physiological factors for the improvement of hiPSC neural in vitro models.

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Citations

Nov 17, 2020·Frontiers in Cell and Developmental Biology·Julia IzsakSebastian Illes
Mar 28, 2021·Developmental Neurobiology·Wai-Kit ChanDavid J Price
Apr 10, 2021·APL Bioengineering·Danielle WarrenJeremy M Crook

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Methods Mentioned

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Software Mentioned

_ Rack Channel
SPANNER
IGOR Pro
MATLAB
SPANNER Medical
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GraphPad Prism

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