scholarly journals Cerebral organoids: a promising model in cellular technologies

2018 ◽  
Vol 22 (2) ◽  
pp. 168-178
Author(s):  
T. A. Shnaider
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Brain Region ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Brain Regions ◽  
Cortical Plate ◽  
Successful Implementation ◽  
Human Pluripotent Stem Cell ◽  
Long Distance

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.

scholarly journals Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

2020 ◽  
Vol 132 ◽  
pp. 104042 ◽  
Author(s):  
Raleigh M. Linville ◽  
Diego Arevalo ◽  
Joanna C. Maressa ◽  
Nan Zhao ◽  
Peter C. Searson
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Cell Models ◽  
Induced Pluripotent ◽  
Stem Cell Models ◽  
Brain Angiogenesis

Convergence of human pluripotent stem cell, organoid, and genome editing technologies

2021 ◽  
pp. 153537022098580
Author(s):  
Lin Wang ◽  
Zhaohui Ye ◽  
Yoon-Young Jang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Genome Editing ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Experimental Models ◽  
Human Pluripotent Stem Cell ◽  
Research Areas ◽  
Technological Advances

The last decade has seen many exciting technological breakthroughs that greatly expanded the toolboxes for biological and biomedical research, yet few have had more impact than induced pluripotent stem cells and modern-day genome editing. These technologies are providing unprecedented opportunities to improve physiological relevance of experimental models, further our understanding of developmental processes, and develop novel therapies. One of the research areas that benefit greatly from these technological advances is the three-dimensional human organoid culture systems that resemble human tissues morphologically and physiologically. Here we summarize the development of human pluripotent stem cells and their differentiation through organoid formation. We further discuss how genetic modifications, genome editing in particular, were applied to answer basic biological and biomedical questions using organoid cultures of both somatic and pluripotent stem cell origins. Finally, we discuss the potential challenges of applying human pluripotent stem cell and organoid technologies for safety and efficiency evaluation of emerging genome editing tools.

scholarly journals Human Pluripotent Stem Cell-Derived Cardiac Cells: Application in Disease Modeling, Cell Therapy, and Drug Discovery

2021 ◽  
Vol 9 ◽  
Author(s):  
Juan Huang ◽  
Qi Feng ◽  
Li Wang ◽  
Bingying Zhou
Keyword(s):  
Stem Cell ◽  
Drug Discovery ◽  
Cell Therapy ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Cardiac Cells ◽  
Cardiac Diseases ◽  
Human Pluripotent Stem Cell ◽  
Species Specific

Cardiac diseases are the leading cause of deaths worldwide; however, to date, there has been limited progress in the development of therapeutic options for these conditions. Animal models have been the most extensively studied methods to recapitulate a wide variety of cardiac diseases, but these models exhibit species-specific differences in physiology, metabolism and genetics, which lead to inaccurate and unpredictable drug safety and efficacy results, resulting in drug attrition. The development of human pluripotent stem cell (hPSC) technology in theory guarantees an unlimited source of human cardiac cells. These hPSC-derived cells are not only well suited for traditional two-dimensional (2-D) monoculture, but also applicable to more complex systems, such as three-dimensional (3-D) organoids, tissue engineering and heart on-a-chip. In this review, we discuss the application of hPSCs in heart disease modeling, cell therapy, and next-generation drug discovery. While the hPSC-related technologies still require optimization, their advances hold promise for revolutionizing cell-based therapies and drug discovery.

scholarly journals Cardiac Tissues From Stem Cells

2021 ◽  
Vol 128 (6) ◽  
pp. 775-801
Author(s):  
Giulia Campostrini ◽  
Laura M. Windt ◽  
Berend J. van Meer ◽  
Milena Bellin ◽  
Christine L. Mummery
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Cell Types ◽  
The Body ◽  
Current Status ◽  
Human Pluripotent Stem Cell ◽  
3 Dimensional

The ability of human pluripotent stem cells to form all cells of the body has provided many opportunities to study disease and produce cells that can be used for therapy in regenerative medicine. Even though beating cardiomyocytes were among the first cell types to be differentiated from human pluripotent stem cell, cardiac applications have advanced more slowly than those, for example, for the brain, eye, and pancreas. This is, in part, because simple 2-dimensional human pluripotent stem cell cardiomyocyte cultures appear to need crucial functional cues normally present in the 3-dimensional heart structure. Recent tissue engineering approaches combined with new insights into the dialogue between noncardiomyocytes and cardiomyocytes have addressed and provided solutions to issues such as cardiomyocyte immaturity and inability to recapitulate adult heart values for features like contraction force, electrophysiology, or metabolism. Three-dimensional bioengineered heart tissues are thus poised to contribute significantly to disease modeling, drug discovery, and safety pharmacology, as well as provide new modalities for heart repair. Here, we review the current status of 3-dimensional engineered heart tissues.

scholarly journals SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function

2020 ◽  
Author(s):  
Silvia Marchiano ◽  
Tien-Ying Hsiang ◽  
Ty Higashi ◽  
Akshita Khanna ◽  
Hans Reinecke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Cardiac Cells ◽  
Cardiac Complications ◽  
The Novel ◽  
Human Pluripotent Stem Cell ◽  
Viral Receptor ◽  
Cardiac Symptoms ◽  
Improving Patient Care

AbstractGlobal health has been threatened by the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2)1. Although considered primarily a respiratory infection, many COVID-19 patients also suffer severe cardiovascular disease2–4. Improving patient care critically relies on understanding if cardiovascular pathology is caused directly by viral infection of cardiac cells or indirectly via systemic inflammation and/or coagulation abnormalities3,5–9. Here we examine the cardiac tropism of SARS-CoV-2 using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and three-dimensional engineered heart tissues (3D-EHTs). We observe that hPSC-CMs express the viral receptor ACE2 and other viral processing factors, and that SARS-CoV-2 readily infects and replicates within hPSC-CMs, resulting in rapid cell death. Moreover, infected hPSC-CMs show a progressive impairment in both electrophysiological and contractile properties. Thus, COVID-19-related cardiac symptoms likely result from a direct cardiotoxic effect of SARS-CoV-2. Long-term cardiac complications might be possible sequelae in patients who recover from this illness.

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 ◽  
...  
Keyword(s):  
Human Brain ◽  
Pluripotent Stem Cell ◽  
Functional Characterization ◽  
Three Dimensional ◽  
Microelectrode Arrays ◽  
Network Activity ◽  
Human Pluripotent Stem Cell ◽  
Network Function ◽  
Brain Models

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.

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