Publications by authors named "Lassi Sukki"

4 Publications

  • Page 1 of 1

Human Neurons Form Axon-Mediated Functional Connections with Human Cardiomyocytes in Compartmentalized Microfluidic Chip.

Int J Mol Sci 2022 Mar 15;23(6). Epub 2022 Mar 15.

Neuro Group, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.

The cardiac autonomic nervous system (cANS) regulates cardiac function by innervating cardiac tissue with axons, and cardiomyocytes (CMs) and neurons undergo comaturation during the heart innervation in embryogenesis. As cANS is essential for cardiac function, its dysfunctions might be fatal; therefore, cardiac innervation models for studying embryogenesis, cardiac diseases, and drug screening are needed. However, previously reported neuron-cardiomyocyte (CM) coculture chips lack studies of functional neuron-CM interactions with completely human-based cell models. Here, we present a novel completely human cell-based and electrophysiologically functional cardiac innervation on a chip in which a compartmentalized microfluidic device, a 3D3C chip, was used to coculture human induced pluripotent stem cell (hiPSC)-derived neurons and CMs. The 3D3C chip enabled the coculture of both cell types with their respective culture media in their own compartments while allowing the neuronal axons to traverse between the compartments via microtunnels connecting the compartments. Furthermore, the 3D3C chip allowed the use of diverse analysis methods, including immunocytochemistry, RT-qPCR and video microscopy. This system resembled the in vivo axon-mediated neuron-CM interaction. In this study, the evaluation of the CM beating response during chemical stimulation of neurons showed that hiPSC-neurons and hiPSC-CMs formed electrophysiologically functional axon-mediated interactions.
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http://dx.doi.org/10.3390/ijms23063148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955890PMC
March 2022

A modular brain-on-a-chip for modelling epileptic seizures with functionally connected human neuronal networks.

Biosens Bioelectron 2020 Nov 26;168:112553. Epub 2020 Aug 26.

NeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. Electronic address:

Epilepsies are a group of neurological disorders characterised by recurrent epileptic seizures. Seizures, defined as abnormal transient discharges of neuronal activity, can affect the entire brain circuitry or remain more focal in the specific brain regions and neuronal networks. Human pluripotent stem cell (hPSC)-derived neurons are a promising option for modelling epilepsies, but as such, they do not model groups of connected neuronal networks or focal seizures. Our solution is a Modular Platform for Epilepsy Modelling In Vitro (MEMO), a lab-on-chip device, in which three hPSC-derived networks are separated by a novel microfluidic cell culture device that allows controlled network-to-network axonal connections through microtunnels. In this study, we show that the neuronal networks formed a functional circuitry that was successfully cultured in MEMO for up to 98 days. The spontaneous neuronal network activities were monitored with an integrated custom-made microelectrode array (MEA). The networks developed spontaneous burst activity that was synchronous both within and between the axonally connected networks, i.e. mimicking both local and circuitry functionality of the brain. A convulsant, kainic acid, increased bursts only in the specifically treated networks. The activity reduction by an anticonvulsant, phenytoin, was also localised to treated networks. Therefore, modelling focal seizures in human neuronal networks is now possible with the developed chip.
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http://dx.doi.org/10.1016/j.bios.2020.112553DOI Listing
November 2020

Co-stimulation with IL-1β and TNF-α induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system.

Sci Rep 2019 11 15;9(1):16944. Epub 2019 Nov 15.

NeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Astrocyte reactivation has been discovered to be an important contributor to several neurological diseases. In vitro models involving human astrocytes have the potential to reveal disease-specific mechanisms of these cells and to advance research on neuropathological conditions. Here, we induced a reactive phenotype in human induced pluripotent stem cell (hiPSC)-derived astrocytes and studied the inflammatory natures and effects of these cells on human neurons. Astrocytes responded to interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) treatment with a typical transition to polygonal morphology and a shift to an inflammatory phenotype characterized by altered gene and protein expression profiles. Astrocyte-secreted factors did not exert neurotoxic effects, whereas they transiently promoted the functional activity of neurons. Importantly, we engineered a novel microfluidic platform designed for investigating interactions between neuronal axons and reactive astrocytes that also enables the implementation of a controlled inflammatory environment. In this platform, selective stimulation of astrocytes resulted in an inflammatory niche that sustained axonal growth, further suggesting that treatment induces a reactive astrocyte phenotype with neurosupportive characteristics. Our findings show that hiPSC-derived astrocytes are suitable for modeling astrogliosis, and the developed in vitro platform provides promising novel tools for studying neuron-astrocyte crosstalk and human brain disease in a dish.
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http://dx.doi.org/10.1038/s41598-019-53414-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858358PMC
November 2019

Optimised PDMS Tunnel Devices on MEAs Increase the Probability of Detecting Electrical Activity from Human Stem Cell-Derived Neuronal Networks.

Front Neurosci 2017 31;11:606. Epub 2017 Oct 31.

NeuroGroup, BioMediTech Institute and Faculty of Medicine and Biosciences, University of Tampere, Tampere, Finland.

Measurement of the activity of human pluripotent stem cell (hPSC)-derived neuronal networks with microelectrode arrays (MEAs) plays an important role in functional brain modelling and in neurotoxicological screening. The previously reported hPSC-derived neuronal networks do not, however, exhibit repeatable, stable functional network characteristics similar to rodent cortical cultures, making the interpretation of results difficult. In earlier studies, microtunnels have been used both to control and guide cell growth and amplify the axonal signals of rodent neurons. The aim of the current study was to develop tunnel devices that would facilitate signalling and/or signal detection in entire hPSC-derived neuronal networks containing not only axons, but also somata and dendrites. Therefore, MEA-compatible polydimethylsiloxane (PDMS) tunnel devices with 8 different dimensions were created. The hPSC-derived neurons were cultured in the tunnel devices on MEAs, and the spontaneous electrical activity of the networks was measured for 5 weeks. Although the tunnel devices improved the signal-to-noise ratio only by 1.3-fold at best, they significantly increased the percentage of electrodes detecting neuronal activity (52-100%) compared with the controls (27%). Significantly higher spike and burst counts were also obtained using the tunnel devices. Neuronal networks inside the tunnels were amenable to pharmacological manipulation. The results suggest that tunnel devices encompassing the entire neuronal network can increase the measured spontaneous activity in hPSC-derived neuronal networks on MEAs. Therefore, they can increase the efficiency of functional studies of hPSC-derived networks on MEAs.
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http://dx.doi.org/10.3389/fnins.2017.00606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671636PMC
October 2017
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