scholarly journals Multiscale 3D phenotyping of human cerebral organoids

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexandre Albanese ◽  
Justin M. Swaney ◽  
Dae Hee Yun ◽  
Nicholas B. Evans ◽  
Jenna M. Antonucci ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Fluorescence Microscopy ◽  
Human Brain ◽  
Spatial Information ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Integrated Technology ◽  
Human Brain Development ◽  
Three Dimensional Models

AbstractBrain organoids grown from human pluripotent stem cells self-organize into cytoarchitectures resembling the developing human brain. These three-dimensional models offer an unprecedented opportunity to study human brain development and dysfunction. Characterization currently sacrifices spatial information for single-cell or histological analysis leaving whole-tissue analysis mostly unexplored. Here, we present the SCOUT pipeline for automated multiscale comparative analysis of intact cerebral organoids. Our integrated technology platform can rapidly clear, label, and image intact organoids. Algorithmic- and convolutional neural network-based image analysis extract hundreds of features characterizing molecular, cellular, spatial, cytoarchitectural, and organoid-wide properties from fluorescence microscopy datasets. Comprehensive analysis of 46 intact organoids and ~ 100 million cells reveals quantitative multiscale “phenotypes" for organoid development, culture protocols and Zika virus infection. SCOUT provides a much-needed framework for comparative analysis of emerging 3D in vitro models using fluorescence microscopy.

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.

ten years of modelling to achieve haemodynamic optimisation of the total cavopulmonary connection

2004 ◽  
Vol 14 (S3) ◽  
pp. 48-52 ◽  
Author(s):  
gabriele dubini ◽  
francesco migliavacca ◽  
giancarlo pennati ◽  
marc r. de leval ◽  
edward l. bove
Keyword(s):  
Fluid Dynamics ◽  
Computational Fluid Dynamics ◽  
Cardiovascular System ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Surgical Reconstruction ◽  
Complex Anatomy ◽  
Recent Developments ◽  
Three Dimensional Models

the techniques of computational fluid dynamics are among the most powerful tools available to engineers dealing with the motion of fluids and the exchange of mass, momentum, and energy. they have recently been shown to have an increasing number of applications to the human cardiovascular system, including the fluid dynamics of surgical reconstruction of congenitally malformed parts of the cardiovascular system. in vitro models are the alternative laboratory tools with which to study fluid dynamics. the advantages of computational fluid dynamics over the in vitro models are the easy quantification of haemodynamic variables, such as rates of flow, pressure, and distribution of shear stress, and changes in geometric and fluid dynamics parameters. furthermore, using computational fluid dynamics allows the development of three-dimensional models to reproduce both the complex anatomy of the investigated region and the details of the surgical reconstruction, especially with the recent developments in magnetic resonance imaging. on the basis of the results, it is possible quantitatively to evaluate the surgical correction. this technology, which benefits greatly from the continuous improvement in hardware and software, enables cardiovascular experts and bioengineers to look at the fluid dynamics of various cardiovascular regions with increasing sophistication.

Three-dimensional models of human brain development

2020 ◽  
pp. 257-278
Author(s):  
Alejandro Lopez-Tobon ◽  
Nicolò Caporale ◽  
Sebastiano Trattaro ◽  
Giuseppe Testa
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Three Dimensional ◽  
Human Brain Development ◽  
Dimensional Models ◽  
Three Dimensional Models

scholarly journals Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Luo ◽  
Peng Li
Keyword(s):  
Human Brain ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Resource Limitation ◽  
In Vitro Models ◽  
Human Brain Tissue ◽  
Self Organized ◽  
Future Direction ◽  
Neural Disorders

AbstractThe sheer complexities of brain and resource limitation of human brain tissue greatly hamper our understanding of the brain disorders and cancers. Recently developed three-dimensional (3D) brain organoids (BOs) are self-organized and spontaneously differentiated from human pluripotent stem cells (hPSCs) in vitro, which exhibit similar features with cell type diversity, structural organization, and functional connectivity as the developing human brain. Based on these characteristics, hPSC-derived BOs (hPDBOs) provide new opportunities to recapitulate the complicated processes during brain development, neurodegenerative disorders, and brain cancers in vitro. In this review, we will provide an overview of existing BO models and summarize the applications of this technology in modeling the neural disorders and cancers. Furthermore, we will discuss the challenges associated with their use as in vitro models for disease modeling and the potential future direction.

scholarly journals Three-Dimensional Models of the Human Brain Development and Diseases

2017 ◽  
Vol 7 (1) ◽  
pp. 1700723 ◽  
Author(s):  
Mehdi Jorfi ◽  
Carla D'Avanzo ◽  
Doo Yeon Kim ◽  
Daniel Irimia
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Three Dimensional ◽  
Human Brain Development ◽  
Dimensional Models ◽  
Three Dimensional Models

scholarly journals In vitro models of the human endometrium: evolution and application for women’s health+

2020 ◽  
Author(s):  
Harriet C Fitzgerald ◽  
Danny J Schust ◽  
Thomas E Spencer
Keyword(s):  
Embryo Implantation ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Human Endometrium ◽  
Placental Development ◽  
Intrauterine Environment ◽  
Evolution And Development ◽  
Three Dimensional Models ◽  
Human Menstrual Cycle

Abstract The endometrium is the inner lining of the uterus that undergoes complex regeneration and differentiation during the human menstrual cycle. The process of endometrial shedding, regeneration, and differentiation is driven by ovarian steroid hormones and prepares the endometrium and intrauterine environment for embryo implantation and pregnancy establishment. Endometrial glands and their secretions are essential for pregnancy establishment, and cross talk between the glandular epithelium and stromal cells appears vital for decidualization and placental development. Despite being crucial, the biology of the human endometrium during pregnancy establishment and most of pregnancy is incomplete, given the ethical and practical limitations of obtaining and studying endometrium from pregnant women. As such, in vitro models of the human endometrium are required to fill significant gaps in understanding endometrial biology. This review is focused on the evolution and development of in vitro three-dimensional models of the human endometrium and provides insight into the challenges and promises of those models to improve women’s reproductive health.

3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas

2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cancer Biology ◽  
Soft Tissues ◽  
Three Dimensional ◽  
3D Culture ◽  
Resistance Mechanisms ◽  
In Vitro Models ◽  
Tumour Spheroids ◽  
Current Therapies

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.

scholarly journals Organoids of the female reproductive tract

2021 ◽  
Vol 99 (4) ◽  
pp. 531-553 ◽  
Author(s):  
Cindrilla Chumduri ◽  
Margherita Y. Turco
Keyword(s):  
Reproductive Tract ◽  
Personalised Medicine ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Experimental Models ◽  
Female Reproductive Tract ◽  
Cellular Heterogeneity ◽  
Dynamic Regulation ◽  
Pregnancy And Childbirth

AbstractHealthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.

scholarly journals Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 141
Author(s):  
Iwona Ziółkowska-Suchanek
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Hypoxia ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Small Cell ◽  
Small Cell Lung ◽  
Multicellular Tumor Spheroid

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.

Integrative analysis of the human brain mural cell transcriptome

2021 ◽  
pp. 0271678X2110137
Author(s):  
Benjamin D Gastfriend ◽  
Koji L Foreman ◽  
Moriah E Katt ◽  
Sean P Palecek ◽  
Eric V Shusta
Keyword(s):  
Human Brain ◽  
Cell Function ◽  
In Vitro Models ◽  
Molecular Characteristics ◽  
Mural Cell ◽  
Mural Cells ◽  
Brain Pericytes ◽  
Mouse Species ◽  
Cell Transcriptome

Brain mural cells, including pericytes and vascular smooth muscle cells, are important for vascular development, blood-brain barrier function, and neurovascular coupling, but the molecular characteristics of human brain mural cells are incompletely characterized. Single cell RNA-sequencing (scRNA-seq) is increasingly being applied to assess cellular diversity in the human brain, but the scarcity of mural cells in whole brain samples has limited their molecular profiling. Here, we leverage the combined power of multiple independent human brain scRNA-seq datasets to build a transcriptomic database of human brain mural cells. We use this combined dataset to determine human-mouse species differences in mural cell transcriptomes, culture-induced dedifferentiation of human brain pericytes, and human mural cell organotypicity, with several key findings validated by RNA fluorescence in situ hybridization. Together, this work improves knowledge regarding the molecular constituents of human brain mural cells, serves as a resource for hypothesis generation in understanding brain mural cell function, and will facilitate comparative evaluation of animal and in vitro models.

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