Concise Review: Modeling Neurodegenerative Diseases with Human Pluripotent Stem Cell‐Derived Microglia
Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain...
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| Vydané v: | Stem cells (Dayton, Ohio) Ročník 37; číslo 6; s. 724 - 730 |
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| Hlavní autori: | , |
| Médium: | Journal Article |
| Jazyk: | English |
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Hoboken, USA
John Wiley & Sons, Inc
01.06.2019
Oxford University Press |
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| ISSN: | 1066-5099, 1549-4918, 1549-4918 |
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| Abstract | Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)‐derived microglia have recently been developed and provide unlimited access to patient‐derived material. In this present study, we give an overview of iPSC‐derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia‐induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient‐specific therapies against neurodegeneration. Stem Cells 2019;37:724–730
Modelling of neurological diseases can be done in mono‐cultures for many readouts, but for authentic modelling of neuron‐microglia interactions such as synapse pruning events it is crucial to use co‐cultures. |
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| AbstractList | Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)-derived microglia have recently been developed and provide unlimited access to patient-derived material. In this present study, we give an overview of iPSC-derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia-induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient-specific therapies against neurodegeneration. Stem Cells 2019;37:724–730 Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)-derived microglia have recently been developed and provide unlimited access to patient-derived material. In this present study, we give an overview of iPSC-derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia-induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient-specific therapies against neurodegeneration. Stem Cells 2019;37:724-730.Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)-derived microglia have recently been developed and provide unlimited access to patient-derived material. In this present study, we give an overview of iPSC-derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia-induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient-specific therapies against neurodegeneration. Stem Cells 2019;37:724-730. Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)‐derived microglia have recently been developed and provide unlimited access to patient‐derived material. In this present study, we give an overview of iPSC‐derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia‐induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient‐specific therapies against neurodegeneration. stem cells 2019;37:724–730 Modelling of neurological diseases can be done in mono‐cultures for many readouts, but for authentic modelling of neuron‐microglia interactions such as synapse pruning events it is crucial to use co‐cultures. Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)‐derived microglia have recently been developed and provide unlimited access to patient‐derived material. In this present study, we give an overview of iPSC‐derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia‐induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient‐specific therapies against neurodegeneration. Stem Cells 2019;37:724–730 Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)‐derived microglia have recently been developed and provide unlimited access to patient‐derived material. In this present study, we give an overview of iPSC‐derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia‐induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient‐specific therapies against neurodegeneration. Stem Cells 2019;37:724–730 Modelling of neurological diseases can be done in mono‐cultures for many readouts, but for authentic modelling of neuron‐microglia interactions such as synapse pruning events it is crucial to use co‐cultures. Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)-derived microglia have recently been developed and provide unlimited access to patient-derived material. In this present study, we give an overview of iPSC-derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia-induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient-specific therapies against neurodegeneration. Stem Cells 2019;37:724-730. |
| Author | Rajendran, Lawrence Haenseler, Walther |
| AuthorAffiliation | 2 UK‐Dementia Research Institute (UK‐DRI), Maurice Wohl Basic & Clinical Neuroscience Institute, Institute of Psychiatry, Psychology, and Neuroscience King's College London London United Kingdom 1 Systems and Cell Biology of Neurodegeneration IREM, University of Zurich Schlieren Switzerland |
| AuthorAffiliation_xml | – name: 1 Systems and Cell Biology of Neurodegeneration IREM, University of Zurich Schlieren Switzerland – name: 2 UK‐Dementia Research Institute (UK‐DRI), Maurice Wohl Basic & Clinical Neuroscience Institute, Institute of Psychiatry, Psychology, and Neuroscience King's College London London United Kingdom |
| Author_xml | – sequence: 1 givenname: Walther orcidid: 0000-0003-4868-3704 surname: Haenseler fullname: Haenseler, Walther email: walther.haenseler@irem.uzh.ch organization: IREM, University of Zurich – sequence: 2 givenname: Lawrence surname: Rajendran fullname: Rajendran, Lawrence email: lawrence.rajendran@kcl.ac.uk organization: King's College London |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30801863$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer Disease - therapy Alzheimer's disease Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - genetics Amyotrophic Lateral Sclerosis - metabolism Amyotrophic Lateral Sclerosis - pathology Amyotrophic Lateral Sclerosis - therapy Brain Cell lines Cell- and Tissue-Based Therapy - methods Coculture Techniques Dementia disorders Disease control Drug screening Embryonic Stem Cells/Induced Pluripotent Stem Cells Experimental models Frontotemporal dementia Frontotemporal Dementia - genetics Frontotemporal Dementia - metabolism Frontotemporal Dementia - pathology Frontotemporal Dementia - therapy Gene Knockout Techniques Genetic Engineering - methods Glia High-Throughput Screening Assays Humans Immunology Induced pluripotent stem cells Induced Pluripotent Stem Cells - drug effects Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - pathology Inflammation Macrophages Microglia Microglia - drug effects Microglia - metabolism Microglia - pathology Modelling Models, Biological Monoculture Movement disorders Myeloid cells Neurodegeneration Neurodegenerative diseases Neuroimmune Neurological diseases Neurons - drug effects Neurons - metabolism Neurons - pathology Neuroprotective Agents - therapeutic use Nootropic Agents - therapeutic use Parkinson Disease - genetics Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson Disease - therapy Parkinson's disease Phenotyping Pluripotency Stem cells Synapses Yolk sac cell |
| Title | Concise Review: Modeling Neurodegenerative Diseases with Human Pluripotent Stem Cell‐Derived Microglia |
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