Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration

Human cerebral organoids derived from induced pluripotent stem cells (iPSCs) provide novel tools for recapitulating the cytoarchitecture of the human brain and for studying biological mechanisms of neurological disorders. However, the heterotypic interactions of neurovascular units, composed of neur...

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Main Authors: Liqing Song, Yuanwei Yan, Mark Marzano, Yan Li
Format: Article
Language:English
Published: MDPI AG 2019-04-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/4/299
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author Liqing Song
Yuanwei Yan
Mark Marzano
Yan Li
author_facet Liqing Song
Yuanwei Yan
Mark Marzano
Yan Li
author_sort Liqing Song
collection DOAJ
description Human cerebral organoids derived from induced pluripotent stem cells (iPSCs) provide novel tools for recapitulating the cytoarchitecture of the human brain and for studying biological mechanisms of neurological disorders. However, the heterotypic interactions of neurovascular units, composed of neurons, pericytes (i.e., the tissue resident mesenchymal stromal cells), astrocytes, and brain microvascular endothelial cells, in brain-like tissues are less investigated. In addition, most cortical organoids lack a microglia component, the resident immune cells in the brain. Impairment of the blood-brain barrier caused by improper crosstalk between neural cells and vascular cells is associated with many neurodegenerative disorders. Mesenchymal stem cells (MSCs), with a phenotype overlapping with pericytes, have promotion effects on neurogenesis and angiogenesis, which are mainly attributed to secreted growth factors and extracellular matrices. As the innate macrophages of the central nervous system, microglia regulate neuronal activities and promote neuronal differentiation by secreting neurotrophic factors and pro-/anti-inflammatory molecules. Neuronal-microglia interactions mediated by chemokines signaling can be modulated in vitro for recapitulating microglial activities during neurodegenerative disease progression. In this review, we discussed the cellular interactions and the physiological roles of neural cells with other cell types including endothelial cells and microglia based on iPSC models. The therapeutic roles of MSCs in treating neural degeneration and pathological roles of microglia in neurodegenerative disease progression were also discussed.
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spelling doaj.art-f57433a830c94bc09f59d127f6a6915a2023-09-03T05:11:11ZengMDPI AGCells2073-44092019-04-018429910.3390/cells8040299cells8040299Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for NeurodegenerationLiqing Song0Yuanwei Yan1Mark Marzano2Yan Li3Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, 2525 Pottsdamer St., Tallahassee, FL 32310, USADepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, 2525 Pottsdamer St., Tallahassee, FL 32310, USADepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, 2525 Pottsdamer St., Tallahassee, FL 32310, USADepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, 2525 Pottsdamer St., Tallahassee, FL 32310, USAHuman cerebral organoids derived from induced pluripotent stem cells (iPSCs) provide novel tools for recapitulating the cytoarchitecture of the human brain and for studying biological mechanisms of neurological disorders. However, the heterotypic interactions of neurovascular units, composed of neurons, pericytes (i.e., the tissue resident mesenchymal stromal cells), astrocytes, and brain microvascular endothelial cells, in brain-like tissues are less investigated. In addition, most cortical organoids lack a microglia component, the resident immune cells in the brain. Impairment of the blood-brain barrier caused by improper crosstalk between neural cells and vascular cells is associated with many neurodegenerative disorders. Mesenchymal stem cells (MSCs), with a phenotype overlapping with pericytes, have promotion effects on neurogenesis and angiogenesis, which are mainly attributed to secreted growth factors and extracellular matrices. As the innate macrophages of the central nervous system, microglia regulate neuronal activities and promote neuronal differentiation by secreting neurotrophic factors and pro-/anti-inflammatory molecules. Neuronal-microglia interactions mediated by chemokines signaling can be modulated in vitro for recapitulating microglial activities during neurodegenerative disease progression. In this review, we discussed the cellular interactions and the physiological roles of neural cells with other cell types including endothelial cells and microglia based on iPSC models. The therapeutic roles of MSCs in treating neural degeneration and pathological roles of microglia in neurodegenerative disease progression were also discussed.https://www.mdpi.com/2073-4409/8/4/299pluripotent stem cellsheterotypicmicrogliaendothelialneural-vascular interactionsmesenchymal stem cells
spellingShingle Liqing Song
Yuanwei Yan
Mark Marzano
Yan Li
Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration
Cells
pluripotent stem cells
heterotypic
microglia
endothelial
neural-vascular interactions
mesenchymal stem cells
title Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration
title_full Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration
title_fullStr Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration
title_full_unstemmed Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration
title_short Studying Heterotypic Cell–Cell Interactions in the Human Brain Using Pluripotent Stem Cell Models for Neurodegeneration
title_sort studying heterotypic cell cell interactions in the human brain using pluripotent stem cell models for neurodegeneration
topic pluripotent stem cells
heterotypic
microglia
endothelial
neural-vascular interactions
mesenchymal stem cells
url https://www.mdpi.com/2073-4409/8/4/299
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AT yuanweiyan studyingheterotypiccellcellinteractionsinthehumanbrainusingpluripotentstemcellmodelsforneurodegeneration
AT markmarzano studyingheterotypiccellcellinteractionsinthehumanbrainusingpluripotentstemcellmodelsforneurodegeneration
AT yanli studyingheterotypiccellcellinteractionsinthehumanbrainusingpluripotentstemcellmodelsforneurodegeneration