Title: 3D bioprinting of human neural tissues with functional connectivity
Legend: Bottom – 3D printed human cortical-striatal tissue showed unidirectional projection. Red staining with SMI321, indicating the cortical axon projection; Green staining with ChrR2-EYFP, indicating striatal cells; Blue is cell nucleus staining
Citation: Yan, Y., Li, X., Gao, Y., Mathivanan, S., Kong, L., Tao, Y., Dong, Y., Li, X., Bhattacharyya, A., Zhao, X., & Zhang, S. C. (2024). 3D bioprinting of human neural tissues with functional connectivity. Cell stem cell, 31(2), 260–274.e7. https://doi.org/10.1016/j.stem.2023.12.009
Abstract: Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. We developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter. The printed neuronal progenitors differentiate into neurons and form functional neural circuits within and between tissue layers with specificity within weeks, evidenced by the cortical-to-striatal projection, spontaneous synaptic currents, and synaptic response to neuronal excitation. Printed astrocyte progenitors develop into mature astrocytes with elaborated processes and form functional neuron-astrocyte networks, indicated by calcium flux and glutamate uptake in response to neuronal excitation under physiological and pathological conditions. These designed human neural tissues will likely be useful for understanding the wiring of human neural networks, modeling pathological processes, and serving as platforms for drug testing.
Investigator: Su-Chun Zhang, MD, PhD
About the Lab: The Zhang laboratory intends to answer how functionally diversified neuronal and glial subtypes are born in the making of our human brain. They have developed models of neural differentiation from mouse, monkey, and human embryonic stem cells (ESCs) that recapitulate key events occurring during early embryo development, including induction of multipotential neuroepithelial cells that form neural tube-like structures, patterning of region-specific neural progenitors, and generation of neurons and glia with particular transmitter or functional phenotypes. In parallel, they are building transgenic human ESC lines with regulatable gene expression. Together, they are dissecting biochemical interactions underlying the cellular differentiation processes under defined conditions. Such studies will hopefully bridge what we have learned from animal studies to human biology.