scholarly journals Functional Characterization of Human Pluripotent Stem Cell-Derived Models of the Brain with Microelectrode Arrays

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 106
Author(s):  
Anssi Pelkonen ◽  
Cristiana Pistono ◽  
Pamela Klecki ◽  
Mireia Gómez-Budia ◽  
Antonios Dougalis ◽  
...  

Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tanja Hyvärinen ◽  
Anu Hyysalo ◽  
Fikret Emre Kapucu ◽  
Laura Aarnos ◽  
Andrey Vinogradov ◽  
...  

AbstractHuman pluripotent stem cell (hPSC)-derived neurons provide exciting opportunities for in vitro modeling of neurological diseases and for advancing drug development and neurotoxicological studies. However, generating electrophysiologically mature neuronal networks from hPSCs has been challenging. Here, we report the differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate. We apply microelectrode array (MEA) measurements to assess network events and compare the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. The hPSC-derived networks developed synchronous activity, which involved glutamatergic and GABAergic inputs, recapitulating the classical cortical activity also observed in rodent counterparts. Principal component analysis (PCA) based on spike rates, network synchronization and burst features revealed the segregation of hPSC-derived and rat network recordings into different clusters, reflecting the species-specific and maturation state differences between the two networks. Overall, hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, which validates their applicability as a human-specific model for pharmacological studies and modeling network dysfunctions.


2018 ◽  
Vol 22 (2) ◽  
pp. 168-178
Author(s):  
T. A. Shnaider

The development of the human brain is a complex multi-stage process including the formation of various types of neural cells and their interactions. Many fundamental mechanisms of neurogenesis have been established due to the studying of model animals. However, significant differences in the brain structure compared to other animals do not allow considering all aspects of the human brain formation, which could play the main role in the development of unique cognitive abilities for human. Four years ago, Lancaster’s group elaborated human pluripotent stem cell-derived three-dimensional cerebral organoid technology, which opened a unique opportunity for researchers to model early stages of human neurogenesis in vitro. Cerebral organoids closely remodel many endogenous brain regions with specific cell composition like ventricular zone with radial glia, choroid plexus, and cortical plate with upper and deeper-layer neurons. Moreover, human brain development includes interactions between different brain regions. Generation of hybrid three-dimensional cerebral organoids with different brain region identity allows remodeling some of them, including long-distance neuronal migration or formation of major axonal tracts. In this review, we consider the technology of obtaining human pluripotent stem cell-derived three-dimensional cerebral organoids with different modifications and with different brain region identity. In addition, we discuss successful implementation of this technology in fundamental and applied research like modeling of different neurodevelopmental disorders and drug screening. Finally, we regard existing problems and prospects for development of human pluripotent stem cell-derived threedimensional cerebral organoid technology.


2020 ◽  
Vol 77 (7) ◽  
pp. 745 ◽  
Author(s):  
Annie Kathuria ◽  
Kara Lopez-Lengowski ◽  
Smita S. Jagtap ◽  
Donna McPhie ◽  
Roy H. Perlis ◽  
...  

2015 ◽  
Vol 9 (7-8) ◽  
pp. 684-694 ◽  
Author(s):  
Tom Dunkley ◽  
Veronica Costa ◽  
Arno Friedlein ◽  
Sebastian Lugert ◽  
Stefan Aigner ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186147 ◽  
Author(s):  
Benjamin M. Bader ◽  
Anne Steder ◽  
Anders Bue Klein ◽  
Bente Frølund ◽  
Olaf H. U. Schroeder ◽  
...  

2020 ◽  
Vol 132 ◽  
pp. 104042 ◽  
Author(s):  
Raleigh M. Linville ◽  
Diego Arevalo ◽  
Joanna C. Maressa ◽  
Nan Zhao ◽  
Peter C. Searson

2019 ◽  
Vol 7 (1) ◽  
pp. 347-361 ◽  
Author(s):  
Haishuang Lin ◽  
Qian Du ◽  
Qiang Li ◽  
Ou Wang ◽  
Zhanqi Wang ◽  
...  

3D thermoreversible PNIPAAm-PEG hydrogels are used for scalable production of human pluripotent stem cell-derived vascular smooth muscle cells.


Materials ◽  
2019 ◽  
Vol 12 (17) ◽  
pp. 2762 ◽  
Author(s):  
Ruimin Shi ◽  
Bukang Wang ◽  
Zhiwei Yan ◽  
Zongyan Wang ◽  
Lei Dong

In order to explore the relationship between the surface topography parameters and friction properties of a rough contact interface under fluid dynamic pressure lubrication conditions, friction experiments were carried out. The three-dimensional surface topography of specimens was measured and characterized with a profile microscopy measuring system and scanning electron microscope. The friction coefficient showed a trend of decreasing first and then increasing with the increase in some surface topography parameters at lower pressure, such as the surface height arithmetic mean Sa, surface height distribution kurtosis Sku, surface volume average volume Vvv, and surface center area average void volume Vvc, which are the ISO 25178 international standard parameters. The effects of surface topographic parameters on friction were analyzed and the wear mechanism of the worn surface was presented. The wear characteristics of the samples were mainly characterized as strain fatigue, grinding, and scraping. The results provide a theoretical basis for the functional characterization of surface topography.


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