scholarly journals Trace elements during primordial plexiform network formation in human cerebral organoids

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2927 ◽  
Author(s):  
Rafaela C. Sartore ◽  
Simone C. Cardoso ◽  
Yury V.M. Lages ◽  
Julia M. Paraguassu ◽  
Mariana P. Stelling ◽  
...  
Keyword(s):  
Trace Elements ◽  
Human Brain ◽  
Cell Biology ◽  
Network Formation ◽  
Interaction Patterns ◽  
Human Brain Tissue ◽  
Concentration Gradients ◽  
Human Telencephalon

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon developmentin vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.

scholarly journals Trace elements during primordial plexiform network formation in human cerebral organoids

2016 ◽  
Author(s):  
Rafaela C Sartore ◽  
Simone C Cardoso ◽  
Yuri V Lages ◽  
Julia M Paraguassu ◽  
Rodrigo F Madeiro da Costa ◽  
...  
Keyword(s):  
Trace Elements ◽  
Human Brain ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Network Formation ◽  
Biological Processes ◽  
Human Brain Tissue ◽  
Human Brain Development ◽  
Calcium Iron ◽  
Human Telencephalon

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development. In the present work, we exposed cerebral organoids derived from human pluripotent stem cells to synchrotron radiation in order to measure how biologically valuable micronutrients are incorporated and distributed in the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves calcium, iron, phosphorus, potassium, sulfur, and zinc. Local trends in concentrations suggest a switch from passive to actively mediated transport across cell membranes. Finally, correlational analysis for pairs of elements shows spatially conserved patterns, suggesting they may physically associate, be stored in similar compartments or used in related biological processes. These findings might reflect which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.

scholarly journals Trace elements during primordial plexiform network formation in human cerebral organoids

2016 ◽  
Author(s):  
Rafaela C Sartore ◽  
Simone C Cardoso ◽  
Yuri V Lages ◽  
Julia M Paraguassu ◽  
Rodrigo F Madeiro da Costa ◽  
...  
Keyword(s):  
Trace Elements ◽  
Human Brain ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Network Formation ◽  
Biological Processes ◽  
Human Brain Tissue ◽  
Human Brain Development ◽  
Calcium Iron ◽  
Human Telencephalon

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development. In the present work, we exposed cerebral organoids derived from human pluripotent stem cells to synchrotron radiation in order to measure how biologically valuable micronutrients are incorporated and distributed in the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves calcium, iron, phosphorus, potassium, sulfur, and zinc. Local trends in concentrations suggest a switch from passive to actively mediated transport across cell membranes. Finally, correlational analysis for pairs of elements shows spatially conserved patterns, suggesting they may physically associate, be stored in similar compartments or used in related biological processes. These findings might reflect which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.

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.

In situ generation of human brain organoids on a micropillar array

Lab on a Chip ◽  
2017 ◽  
Vol 17 (17) ◽  
pp. 2941-2950 ◽  
Author(s):  
Yujuan Zhu ◽  
Li Wang ◽  
Hao Yu ◽  
Fangchao Yin ◽  
Yaqing Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Brain ◽  
Pluripotent Stem Cells ◽  
3D Culture ◽  
In Situ Generation ◽  
Induced Pluripotent ◽  
High Throughput Manner

We present a simple and high throughput manner to generate brain organoids in situ from human induced pluripotent stem cells on micropillar arrays and to investigate long-term brain organogenesis in 3D culture in vitro.

Long-term functional maintenance of primary human hepatocytes in vitro

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. 399-402 ◽  
Author(s):  
Chengang Xiang ◽  
Yuanyuan Du ◽  
Gaofan Meng ◽  
Liew Soon Yi ◽  
Shicheng Sun ◽  
...  
Keyword(s):  
Cell Biology ◽  
Expression Profiles ◽  
Antiviral Drug ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Human Hepatocytes ◽  
Hbv Infection ◽  
Primary Human Hepatocytes

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

Effect of Long-term In Vitro Lithium Exposure on mRNA Levels of Claudin-3, CYP1A1, ABCG2 and GSTM3 Genes in the hCMEC/D3 Human Brain Endothelial Cell Line

2017 ◽  
Vol 42 (6) ◽  
pp. 1013-1017 ◽  
Author(s):  
Ramzi Shawahna ◽  
Kayathiri Ganeshamoorthy ◽  
Luo Huilong ◽  
Jean-Michel Scherrmann ◽  
Pierre-Olivier Couraud ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Human Brain ◽  
Cell Line ◽  
Mrna Levels ◽  
Brain Endothelial Cell ◽  
Endothelial Cell Line

scholarly journals The Age of Brain Organoids: Tailoring Cell Identity and Functionality for Normal Brain Development and Disease Modeling

2021 ◽  
Vol 15 ◽  
Author(s):  
Lisiane O. Porciúncula ◽  
Livia Goto-Silva ◽  
Pitia F. Ledur ◽  
Stevens K. Rehen
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Functional Activity ◽  
Network Formation ◽  
Disease Modeling ◽  
Morphological Data ◽  
Neural Cells ◽  
Normal Brain ◽  
Human Brain Tissue ◽  
Cell Repertoire

Over the past years, brain development has been investigated in rodent models, which were particularly relevant to establish the role of specific genes in this process. However, the cytoarchitectonic features, which determine neuronal network formation complexity, are unique to humans. This implies that the developmental program of the human brain and neurological disorders can only partly be reproduced in rodents. Advancement in the study of the human brain surged with cultures of human brain tissue in the lab, generated from induced pluripotent cells reprogrammed from human somatic tissue. These cultures, termed brain organoids, offer an invaluable model for the study of the human brain. Brain organoids reproduce the cytoarchitecture of the cortex and can develop multiple brain regions and cell types. Integration of functional activity of neural cells within brain organoids with genetic, cellular, and morphological data in a comprehensive model for human development and disease is key to advance in the field. Because the functional activity of neural cells within brain organoids relies on cell repertoire and time in culture, here, we review data supporting the gradual formation of complex neural networks in light of cell maturity within brain organoids. In this context, we discuss how the technology behind brain organoids brought advances in understanding neurodevelopmental, pathogen-induced, and neurodegenerative diseases.

Developing a Model of Human Pluripotent to Hematopoietic Stem Cell Development in Mistrg Mice

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4755-4755
Author(s):  
John Astle ◽  
Yangfei Xiang ◽  
Anthony Rongvaux ◽  
Carla Weibel ◽  
Henchey Elizabeth ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice

Abstract De novo generation of HSCs has been described as a "holy grail" of stem cell biology, however the factors required for converting human pluripotent stem cells (PSCs) to true hematopoietic stem cells (HSCs) capable of robust long-term engraftment have yet to be fully characterized. Two groups have shown that injection of PSCs into immunodeficient mice leads to teratomas containing niches producing hematopoietic progenitors capable of long-term engraftment. Once these hematopoietic progenitors and their microenvironments are better characterized, this system could be used as a model to help direct in vitro differentiation of PSCs to HSCs. Toward this end, we have injected human PSCs into immunodeficient mice expressing human rather than mouse M-CSF, IL-3, GM-CSF, and thrombopoietin, as well as both human and mouse versions of the "don't eat me signal" Sirpa (collectively termed MISTRG mice). These cytokines are known to support different aspects of hematopoiesis, and thrombopoietin in particular has been shown to support HSC maintenance, suggesting these mice may provide a better environment for human PSC-derived HSCs than the more traditional mice used for human HSC engraftment. The majority of teratomas developed so far in MISTRG contain human hematopoietic cells, and the CD34+ population isolated from over half of the teratomas contained hematopoietic colony forming cells by colony forming assay. These findings further corroborate this approach as a viable method for studying human PSC to HSC differentiation. Disclosures No relevant conflicts of interest to declare.

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.

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