scholarly journals Brain organoid formation on decellularized porcine brain ECM hydrogels

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245685
Author(s):  
Robin Simsa ◽  
Theresa Rothenbücher ◽  
Hakan Gürbüz ◽  
Nidal Ghosheh ◽  
Jenny Emneus ◽  
...  
Keyword(s):  
Human Brain ◽  
Dna Content ◽  
Embryonic Stem ◽  
Protein Composition ◽  
Mouse Tumor ◽  
Human Brain Tissue ◽  
Porcine Brain ◽  
Alternative Scaffold ◽  
Brain Organoid

Human brain tissue models such as cerebral organoids are essential tools for developmental and biomedical research. Current methods to generate cerebral organoids often utilize Matrigel as an external scaffold to provide structure and biologically relevant signals. Matrigel however is a nonspecific hydrogel of mouse tumor origin and does not represent the complexity of the brain protein environment. In this study, we investigated the application of a decellularized adult porcine brain extracellular matrix (B-ECM) which could be processed into a hydrogel (B-ECM hydrogel) to be used as a scaffold for human embryonic stem cell (hESC)-derived brain organoids. We decellularized pig brains with a novel detergent- and enzyme-based method and analyzed the biomaterial properties, including protein composition and content, DNA content, mechanical characteristics, surface structure, and antigen presence. Then, we compared the growth of human brain organoid models with the B-ECM hydrogel or Matrigel controls in vitro. We found that the native brain source material was successfully decellularized with little remaining DNA content, while Mass Spectrometry (MS) showed the loss of several brain-specific proteins, while mainly different collagen types remained in the B-ECM. Rheological results revealed stable hydrogel formation, starting from B-ECM hydrogel concentrations of 5 mg/mL. hESCs cultured in B-ECM hydrogels showed gene expression and differentiation outcomes similar to those grown in Matrigel. These results indicate that B-ECM hydrogels can be used as an alternative scaffold for human cerebral organoid formation, and may be further optimized for improved organoid growth by further improving protein retention other than collagen after decellularization.

scholarly journals Complex Activity and Short-term Memories in Reciprocally Connected Cerebral Organoids

2021 ◽  
Author(s):  
Tatsuya Osaki ◽  
Yoshiho Ikeuchi
Keyword(s):  
Human Brain ◽  
Three Dimensional ◽  
Oscillatory Activity ◽  
Cellular Functions ◽  
Complex Activity ◽  
Axonal Connections ◽  
Brain Organoid ◽  
External Stimuli ◽  
The Brain

AbstractMacroscopic axonal connections in the human brain distribute information and neuronal activity across the brain. Although this complexity previously hindered elucidation of functional connectivity mechanisms, brain organoid technologies have recently provided novel avenues to investigate human brain function by constructing small segments of the brain in vitro. Here, we describe the neural activity of human cerebral organoids reciprocally connected by a bundle of axons. Compared to conventional organoids, connected organoids produced significantly more intense and complex oscillatory activity. Optogenetic manipulations revealed that the connected organoids could re-play and recapitulate over time temporal patterns found in external stimuli, indicating that the connected organoids were able to form and retain temporal memories. Our findings suggest that connected organoids may serve as powerful tools for investigating the roles of macroscopic circuits in the human brain – allowing researchers to dissect cellular functions in three-dimensional in vitro nervous system models in unprecedented ways.

scholarly journals Human in vitro systems for examining synaptic function and plasticity in the brain

2020 ◽  
Vol 123 (3) ◽  
pp. 945-965 ◽  
Author(s):  
Kevin Lee ◽  
Thomas I.-H. Park ◽  
Peter Heppner ◽  
Patrick Schweder ◽  
Edward W. Mee ◽  
...  
Keyword(s):  
Animal Models ◽  
Human Brain ◽  
Brain Tissue ◽  
Human Brain Tissue ◽  
Adult Human Brain ◽  
Adult Human ◽  
Human Neurons ◽  
In Vitro Systems ◽  
Human Neuron

The human brain shows remarkable complexity in its cellular makeup and function, which are distinct from nonhuman species, signifying the need for human-based research platforms for the study of human cellular neurophysiology and neuropathology. However, the use of adult human brain tissue for research purposes is hampered by technical, methodological, and accessibility challenges. One of the major problems is the limited number of in vitro systems that, in contrast, are readily available from rodent brain tissue. With recent advances in the optimization of protocols for adult human brain preparations, there is a significant opportunity for neuroscientists to validate their findings in human-based systems. This review addresses the methodological aspects, advantages, and disadvantages of human neuron in vitro systems, focusing on the unique properties of human neurons and synapses in neocortical microcircuits. These in vitro models provide the incomparable advantage of being a direct representation of the neurons that have formed part of the human brain until the point of recording, which cannot be replicated by animal models nor human stem-cell systems. Important distinct cellular mechanisms are observed in human neurons that may underlie the higher order cognitive abilities of the human brain. The use of human brain tissue in neuroscience research also raises important ethical, diversity, and control tissue limitations that need to be considered. Undoubtedly however, these human neuron systems provide critical information to increase the potential of translation of treatments from the laboratory to the clinic in a way animal models are failing to provide.

scholarly journals Challenges in Modeling Human Neural Circuit Formation via Brain Organoid Technology

2020 ◽  
Vol 14 ◽  
Author(s):  
Takeshi K. Matsui ◽  
Yuichiro Tsuru ◽  
Ken-ichiro Kuwako
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Neural Circuit ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Neural Lineage ◽  
Human Brain Development ◽  
Brain Organoid ◽  
Circuit Formation

Human brain organoids are three-dimensional self-organizing tissues induced from pluripotent cells that recapitulate some aspects of early development and some of the early structure of the human brain in vitro. Brain organoids consist of neural lineage cells, such as neural stem/precursor cells, neurons, astrocytes and oligodendrocytes. Additionally, brain organoids contain fluid-filled ventricle-like structures surrounded by a ventricular/subventricular (VZ/SVZ) zone-like layer of neural stem cells (NSCs). These NSCs give rise to neurons, which form multiple outer layers. Since these structures resemble some aspects of structural arrangements in the developing human brain, organoid technology has attracted great interest in the research fields of human brain development and disease modeling. Developmental brain disorders have been intensely studied through the use of human brain organoids. Relatively early steps in human brain development, such as differentiation and migration, have also been studied. However, research on neural circuit formation with brain organoids has just recently began. In this review, we summarize the current challenges in studying neural circuit formation with organoids and discuss future perspectives.

scholarly journals TMOD-12. THE ROLE OF INTEGRIN α V AND CD44 IN GBM MIGRATION USING HUMAN ORGANOTYPIC SLICES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi265-vi265
Author(s):  
Zev Binder ◽  
Sarah Hyun Ji Kim ◽  
Pei-Hsun Wu ◽  
Anjil Giri ◽  
Gary Gallia ◽  
...  
Keyword(s):  
Human Brain ◽  
Cell Motility ◽  
Brain Tissue ◽  
Brain Slices ◽  
Model System ◽  
Model Systems ◽  
In Vivo Model ◽  
Human Brain Tissue

Abstract Current model systems used for GBM research include traditional in vitro cell line-based assays and in vivo animal studies. In vitro model systems offer the advantages of being easy to use, relatively inexpensive, and fast growing. However, these models lack key elements of the pathology they are attempting to model, including the biochemical and biophysical microenvironment and three-dimensional structure inherent to human brain tissue. In vivo model systems address these limitations, but have restrictions of their own. Species differences may result in non-applicable results and animal experiments are often not designed like clinical trials. Evidence of the limitations of current GBM models is found in the disparity between basic research findings and successful new treatments for GBMs in the clinic. Here we present an alternative model system for the study of human GBM cell motility and invasion, which features advantages of both in vitro and in vivo model systems. Using human organotypic brain slices as scaffolding for tumor growth, we explored the dynamic process of GBM cell invasion within human brain tissue. To demonstrate the utility of the model system, we investigated the effects of depletion of integrin α V (ITGAV) and CD44 on GBM cell motility. These two cell-surface proteins have been identified to have key functions in GBM cell motility. However, knockdown of ITGAV had little effect on tumor cell motility in organotypics while CD44 knockdown significantly reduced cell movement. Finally, we compare motility results from cells in human brain slices to those from cells growing on standard Matrigel and in mouse brain organotypics. We found significant differences in motility depending on the substrate in which the cells were moving. Our findings highlight the physiologic characteristics of human brain organotypics and demonstrate the use of real-time imaging in the ex vivo system.

scholarly journals Applications of brain organoids in neurodevelopment and neurological diseases

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Nan Sun ◽  
Xiangqi Meng ◽  
Yuxiang Liu ◽  
Dan Song ◽  
Chuanlu Jiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Brain ◽  
Neurological Diseases ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Cell Types ◽  
Current State ◽  
Spatiotemporal Process ◽  
Brain Organoid

AbstractA brain organoid is a self-organizing three-dimensional tissue derived from human embryonic stem cells or pluripotent stem cells and is able to simulate the architecture and functionality of the human brain. Brain organoid generation methods are abundant and continue to improve, and now, an in vivo vascularized brain organoid has been encouragingly reported. The combination of brain organoids with immune-staining and single-cell sequencing technology facilitates our understanding of brain organoids, including the structural organization and the diversity of cell types. Recent publications have reported that brain organoids can mimic the dynamic spatiotemporal process of early brain development, model various human brain disorders, and serve as an effective preclinical platform to test and guide personalized treatment. In this review, we introduce the current state of brain organoid differentiation strategies, summarize current progress and applications in the medical domain, and discuss the challenges and prospects of this promising technology.

scholarly journals Organoids: the third dimension of human brain development and disease

2021 ◽  
Author(s):  
Georgia Kouroupi ◽  
Kanella Prodromidou ◽  
Florentia Papastefanaki ◽  
Era Taoufik ◽  
Rebecca Matsas
Keyword(s):  
Stem Cells ◽  
Human Brain ◽  
Brain Development ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Two Dimensional ◽  
The Third ◽  
Human Brain Development ◽  
Third Dimension

Stem cell technologies have opened up new avenues in the study of human biology and disease. Especially, the advent of human embryonic stem cells followed by reprograming technologies for generation of induced pluripotent stem cells have instigated studies for modeling human brain development and disease by providing a means to simulate a human tissue with otherwise limited or no accessibility to researchers. Brain development is a complex process achieved in a remarkably controlled spatial and temporal manner through coordinated cellular and molecular events. In vitro models aim to mimic these processes and recapitulate brain organogenesis. Initially, two-dimensional neural cultures presented an innovative landmark for investigating human neuronal and, more recently, glial biology as well as for modeling brain neurodevelopmental and neurodegenerative diseases. The establishment of three-dimensional cultures in the form of brain organoids was an equally important milestone in the field. Brain organoids mimic more closely the in vivo tissue composition and architecture and are more physiologically relevant than monolayer cultures. They therefore represent a more realistic cellular environment for modeling the cell biology and pathology of the nervous system. Here we highlight the journey to recapitulate human brain development and disease in-a-dish, starting from two-dimensional in vitro systems up to the third dimension provided by brain organoids. We discuss the potential of these approaches for modeling human brain development and evolution and their promise for understanding and treating brain disease.

scholarly journals In situ impedance measurements on postmortem porcine brain

2020 ◽  
Author(s):  
Lucas Poßner ◽  
Matthias Laukner ◽  
Florian Wilhelmy ◽  
Dirk Lindner ◽  
Uwe Pliquett ◽  
...  
Keyword(s):  
Experimental Study ◽  
White Matter ◽  
Human Brain ◽  
Brain Tissue ◽  
Human Brain Tissue ◽  
Experimental Conditions ◽  
Impedance Measurements ◽  
Porcine Brain

AbstractThe paper presents an experimental study where the distinctness of grey and white matter of an in situ postmortem porcine brain by impedance measurements is investigated. Experimental conditions that would allow to conduct the same experiment on in vivo human brain tissue are replicated.https://doi.org/10.1515/cdbme-2019-XXXX

Nonlinear Constitutive Relations for Human Brain Tissue

1978 ◽  
Vol 100 (1) ◽  
pp. 44-48 ◽  
Author(s):  
M. R. Pamidi ◽  
S. H. Advani
Keyword(s):  
Head Injury ◽  
Human Brain ◽  
Brain Tissue ◽  
Constitutive Relations ◽  
Continuum Models ◽  
Human Brain Tissue ◽  
Model Predictions ◽  
Energy Principles ◽  
Nonlinear Constitutive Relations

Head injury modeling studies warrant detailed investigations into the rheological behavior of brain tissue. This paper deals with the development of the concept of a power function and employs energy principles to derive nonlinear constitutive relations for human brain tissue. Nonlinear discrete and continuum models are constructed and it is found that the model predictions compare well with experimentally determined in-vitro properties of human brain tissue under uniaxial loading conditions.

scholarly journals Inhibition and oscillations in the human brain tissue in vitro

2019 ◽  
Vol 125 ◽  
pp. 198-210 ◽  
Author(s):  
Liset Menendez de la Prida ◽  
Gilles Huberfeld
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Human Brain Tissue

Rheological Response of Human Brain Tissue in Shear

1972 ◽  
Vol 94 (4) ◽  
pp. 905-911 ◽  
Author(s):  
L. Z. Shuck ◽  
S. H. Advani
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Pure Shear ◽  
Shear Stresses ◽  
Dynamic Shear Modulus ◽  
Elastic Model ◽  
Human Brain Tissue ◽  
Tissue Properties ◽  
Torque Transducer

Head injury is often attributed to transient shear stresses arising from rotation of the brain in the cranial cavity. This paper deals with the experimental determination and analytical characterization of in vitro human brain dynamic constitutive properties in pure shear. A closed loop, feedback torsional system with a self mass cancelling torque transducer is used for the experimental study. Values of the storage and loss components of the dynamic shear modulus are computed and a four parameter, linear, visco-elastic model representing brain tissue properties up to 350 Hz is presented. In addition, failure criterion in terms of limiting strains and strain rates are identified.

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