Research Tools
METHODS FOR PRINTING FUNCTIONAL HUMAN NEURAL TISSUE
WARF: P220006US02
Inventors: Su-Chun Zhang, Yuanwei Yan
The Invention
UW-Madison researchers have developed methods for bioprinting a human neural network in vitro. The inventors’ method fabricates human neural tissues that form a functional neural network within weeks and can be used for drug screening and to study neurological diseases. The inventors have developed a bioink (printing gel) that can be combined with nearly-mature cell progenitors of the desired cell types to form a 3D structure that is amenable for morphological and functional assessment. They worked to formulate a bioink that promotes neural cell survival and differentiation so that the printed neural tissues mature and form functional networks within a month, and the resulting tissues display expected neural function under physiological and pathological conditions for at least two months after preparation.
The inventors generated neuronal progenitors and astrocyte progenitors from human pluripotent stem cells using previous protocols from their and other labs, and confirmed the cell identify using cell surface markers (e.g., NKX2.1 and GABA for GABA interneuron progenitors, FOXG1 and PAX6 for cortical progenitors, S100β and GFAP for astrocyte progenitors, etc). One month after tissue formation, the inventors confirmed that the neurons exhibited pyramidal morphology and formed dendritic structures, and functional assessments confirmed the functional maturation of the cells in the printed tissue, as well as the formation of functional neural networks with functionally integrated astrocytes. The inventors used an inexpensive 3D bioprinter from Cellink Life Sciences, but other and more complex/expensive bioprinters would work too. The inventors further demonstrated the usefulness of the method by using astrocytes from patients with Alexander disease (AxD). As expected, neural tissues printed with AxD astrocytes showed significantly fewer calcium responses than the isogenic control. Their results indicate that the disease-relevant functional phenotypes are detectable in the printed human neural tissues.
The inventors generated neuronal progenitors and astrocyte progenitors from human pluripotent stem cells using previous protocols from their and other labs, and confirmed the cell identify using cell surface markers (e.g., NKX2.1 and GABA for GABA interneuron progenitors, FOXG1 and PAX6 for cortical progenitors, S100β and GFAP for astrocyte progenitors, etc). One month after tissue formation, the inventors confirmed that the neurons exhibited pyramidal morphology and formed dendritic structures, and functional assessments confirmed the functional maturation of the cells in the printed tissue, as well as the formation of functional neural networks with functionally integrated astrocytes. The inventors used an inexpensive 3D bioprinter from Cellink Life Sciences, but other and more complex/expensive bioprinters would work too. The inventors further demonstrated the usefulness of the method by using astrocytes from patients with Alexander disease (AxD). As expected, neural tissues printed with AxD astrocytes showed significantly fewer calcium responses than the isogenic control. Their results indicate that the disease-relevant functional phenotypes are detectable in the printed human neural tissues.
Tech Fields
For current licensing status, please contact Andy DeTienne at [javascript protected email address] or 608-960-9857