scholarly journals Deciphering and reconstitution of positional information in the human brain development

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi-Fan Wang ◽  
Cong Liu ◽  
Peng-Fei Xu
Keyword(s):  
Human Brain ◽  
Neural Development ◽  
Three Dimensional ◽  
Positional Information ◽  
Physiological Level ◽  
Vitro Model ◽  
Brain Organoid ◽  
The Brain

AbstractOrganoid has become a novel in vitro model to research human development and relevant disorders in recent years. With many improvements on the culture protocols, current brain organoids could self-organize into a complicated three-dimensional organization that mimics most of the features of the real human brain at the molecular, cellular, and further physiological level. However, lacking positional information, an important characteristic conveyed by gradients of signaling molecules called morphogens, leads to the deficiency of spatiotemporally regulated cell arrangements and cell–cell interactions in the brain organoid development. In this review, we will overview the role of morphogen both in the vertebrate neural development in vivo as well as the brain organoid culture in vitro, the strategies to apply morphogen concentration gradients in the organoid system and future perspectives of the brain organoid technology.

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 Brain Organoids—A Bottom-Up Approach for Studying Human Neurodevelopment

2019 ◽  
Vol 6 (1) ◽  
pp. 9 ◽  
Author(s):  
Eyal Karzbrun ◽  
Orly Reiner
Keyword(s):  
Human Brain ◽  
Three Dimensional ◽  
Human Stem Cells ◽  
In Vitro Systems ◽  
Brain Organoid ◽  
Specific Disorders ◽  
Bioengineering Techniques ◽  
Human Specific

Brain organoids have recently emerged as a three-dimensional tissue culture platform to study the principles of neurodevelopment and morphogenesis. Importantly, brain organoids can be derived from human stem cells, and thus offer a model system for early human brain development and human specific disorders. However, there are still major differences between the in vitro systems and in vivo development. This is in part due to the challenge of engineering a suitable culture platform that will support proper development. In this review, we discuss the similarities and differences of human brain organoid systems in comparison to embryonic development. We then describe how organoids are used to model neurodevelopmental diseases. Finally, we describe challenges in organoid systems and how to approach these challenges using complementary bioengineering techniques.

The zebrafish brain in research and teaching: a simple in vivo and in vitro model for the study of spontaneous neural activity

2011 ◽  
Vol 35 (2) ◽  
pp. 188-196 ◽  
Author(s):  
R. Vargas ◽  
I. þ. Jóhannesdóttir ◽  
B. Sigurgeirsson ◽  
H. þorsteinsson ◽  
K. Æ. Karlsson
Keyword(s):  
Neural Development ◽  
Neural Circuits ◽  
Brain Slices ◽  
Functional Roles ◽  
Zebrafish Brain ◽  
Vitro Model ◽  
Immunohistochemical Techniques ◽  
Neuronal Groups

Recently, the zebrafish ( Danio rerio ) has been established as a key animal model in neuroscience. Behavioral, genetic, and immunohistochemical techniques have been used to describe the connectivity of diverse neural circuits. However, few studies have used zebrafish to understand the function of cerebral structures or to study neural circuits. Information about the techniques used to obtain a workable preparation is not readily available. Here, we describe a complete protocol for obtaining in vitro and in vivo zebrafish brain preparations. In addition, we performed extracellular recordings in the whole brain, brain slices, and immobilized nonanesthetized larval zebrafish to evaluate the viability of the tissue. Each type of preparation can be used to detect spontaneous activity, to determine patterns of activity in specific brain areas with unknown functions, or to assess the functional roles of different neuronal groups during brain development in zebrafish. The technique described offers a guide that will provide innovative and broad opportunities to beginner students and researchers who are interested in the functional analysis of neuronal activity, plasticity, and neural development in the zebrafish brain.

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.

Local, Three-Dimensional Strain Measurements Within Largely Deformed Extracellular Matrix Constructs

2004 ◽  
Vol 126 (6) ◽  
pp. 699-708 ◽  
Author(s):  
Blayne A. Roeder ◽  
Klod Kokini ◽  
J. Paul Robinson ◽  
Sherry L. Voytik-Harbin
Keyword(s):  
Extracellular Matrix ◽  
Local Level ◽  
Three Dimensional ◽  
Collagen Matrices ◽  
Mechanical Loads ◽  
Strain Measurements ◽  
3D Collagen ◽  
Vitro Model

The ability to create extracellular matrix (ECM) constructs that are mechanically and biochemically similar to those found in vivo and to understand how their properties affect cellular responses will drive the next generation of tissue engineering strategies. To date, many mechanisms by which cells biochemically communicate with the ECM are known. However, the mechanisms by which mechanical information is transmitted between cells and their ECM remain to be elucidated. “Self-assembled” collagen matrices provide an in vitro-model system to study the mechanical behavior of ECM. To begin to understand how the ECM and the cells interact mechanically, the three-dimensional (3D) mechanical properties of the ECM must be quantified at the micro-(local) level in addition to information measured at the macro-(global) level. Here we describe an incremental digital volume correlation (IDVC) algorithm to quantify large (>0.05) 3D mechanical strains in the microstructure of 3D collagen matrices in response to applied mechanical loads. Strain measurements from the IDVC algorithm rely on 3D confocal images acquired from collagen matrices under applied mechanical loads. The accuracy and the precision of the IDVC algorithm was verified by comparing both image volumes collected in succession when no deformation was applied to the ECM (zero strain) and image volumes to which simulated deformations were applied in both 1D and 3D (simulated strains). Results indicate that the IDVC algorithm can accurately and precisely determine the 3D strain state inside largely deformed collagen ECMs. Finally, the usefulness of the algorithm was demonstrated by measuring the microlevel 3D strain response of a collagen ECM loaded in tension.

scholarly journals The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain

2021 ◽  
Vol 7 (26) ◽  
pp. eabg8139
Author(s):  
Cynthia Hajal ◽  
Yoojin Shin ◽  
Leanne Li ◽  
Jean Carlos Serrano ◽  
Tyler Jacks ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Three Dimensional ◽  
Brain Parenchyma ◽  
Cell Axis ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2 ◽  
The Brain

Although brain metastases are common in cancer patients, little is known about the mechanisms of cancer extravasation across the blood-brain barrier (BBB), a key step in the metastatic cascade that regulates the entry of cancer cells into the brain parenchyma. Here, we show, in a three-dimensional in vitro BBB microvascular model, that astrocytes promote cancer cell transmigration via their secretion of C-C motif chemokine ligand 2 (CCL2). We found that this chemokine, produced primarily by astrocytes, promoted the chemotaxis and chemokinesis of cancer cells via their C-C chemokine receptor type 2 (CCR2), with no notable changes in vascular permeability. These findings were validated in vivo, where CCR2-deficient cancer cells exhibited significantly reduced rates of arrest and transmigration in mouse brain capillaries. Our results reveal that the CCL2-CCR2 astrocyte-cancer cell axis plays a fundamental role in extravasation and, consequently, metastasis to the brain.

scholarly journals Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity

RSC Advances ◽  
2019 ◽  
Vol 9 (31) ◽  
pp. 17995-18007 ◽  
Author(s):  
Lingyan Wu ◽  
Gaia Ferracci ◽  
Yan Wang ◽  
Teng Fei Fan ◽  
Nam-Joon Cho ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Colloidal Crystal ◽  
Three Dimensional ◽  
Drug Induced ◽  
Attrition Rates ◽  
Common Causes ◽  
Vitro Model ◽  
Colloidal Crystal Scaffolds

As drug-induced hepatotoxicity represents one of the most common causes of drug failure, three-dimensional in vitro liver platforms represent a fantastic toolbox to predict drug toxicity and reduce in vivo studies and drug attrition rates.

scholarly journals In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices.

1983 ◽  
Vol 97 (5) ◽  
pp. 1648-1652 ◽  
Author(s):  
R Montesano ◽  
L Orci ◽  
P Vassalli
Keyword(s):  
Endothelial Cells ◽  
Three Dimensional ◽  
Collagen Matrix ◽  
Collagen Gels ◽  
Collagen Matrices ◽  
Narrow Lumen ◽  
Capillary Endothelial Cells ◽  
Vitro Model

We have studied the behavior of cloned capillary endothelial cells grown inside a three dimensional collagen matrix. Cell monolayers established on the surface of collagen gels were covered with a second layer of collagen. This induced the monolayers of endothelial cells to reorganize into a network of branching and anastomosing capillary-like tubes. As seen by electron microscopy, the tubes were formed by at least two cells (in transverse sections) delimiting a narrow lumen. In addition, distinct basal lamina material was present between the abluminal face of the endothelial cells and the collagen matrix. These results showed that capillary endothelial cells have the capacity to form vessel-like structures with well-oriented cell polarity in vitro. They also suggest that an appropriate topological relationship of endothelial cells with collagen matrices, similar to that occurring in vivo, has an inducive role on the expression of this potential. This culture system provides a simple in vitro model for studying the factors involved in the formation of new blood vessels (angiogenesis).

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.

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