Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells
The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system...
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| Veröffentlicht in: | International journal of molecular sciences 2021-07, Vol.22 (14), p.7710 |
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| creator | Wu, Ying-Chieh Sonninen, Tuuli-Maria Peltonen, Sanni Koistinaho, Jari Lehtonen, Šárka |
| description | The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer's disease and Parkinson's disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area. |
| doi_str_mv | 10.3390/ijms22147710 |
| format | Article |
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It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer's disease and Parkinson's disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22147710</identifier><identifier>PMID: 34299328</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alzheimer's disease ; Animals ; Blood-brain barrier ; Blood-Brain Barrier - cytology ; Blood-Brain Barrier - metabolism ; Blood-Brain Barrier - pathology ; Brain ; Brain - blood supply ; Brain - cytology ; Brain - metabolism ; Carbon dioxide ; Carbon dioxide removal ; Cell culture ; Cell cycle ; Central nervous system ; Cerebrovascular Circulation ; Drug screening ; Gene expression ; Growth factors ; Homeostasis ; Human influences ; Humans ; Immune clearance ; Immune system ; Immunosuppressive agents ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Induced Pluripotent Stem Cells - pathology ; Membrane permeability ; Metabolites ; Modelling ; Models, Biological ; Neurodegenerative Diseases - metabolism ; Neurodegenerative Diseases - pathology ; Neurological diseases ; Neurotoxins ; Nutrients ; Older people ; Parkinson's disease ; Pathogens ; Pathology ; Permeability ; Pluripotency ; Potassium ; Proteins ; Review ; Stem cells ; Toxins</subject><ispartof>International journal of molecular sciences, 2021-07, Vol.22 (14), p.7710</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-f1c951ff5bd361d03a0b18249c424a7f99c74ae48ac6b91c2b126675fc46be873</citedby><cites>FETCH-LOGICAL-c412t-f1c951ff5bd361d03a0b18249c424a7f99c74ae48ac6b91c2b126675fc46be873</cites><orcidid>0000-0002-1817-1217 ; 0000-0002-5055-9414</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307585/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307585/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34299328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Ying-Chieh</creatorcontrib><creatorcontrib>Sonninen, Tuuli-Maria</creatorcontrib><creatorcontrib>Peltonen, Sanni</creatorcontrib><creatorcontrib>Koistinaho, Jari</creatorcontrib><creatorcontrib>Lehtonen, Šárka</creatorcontrib><title>Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer's disease and Parkinson's disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.</description><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Blood-brain barrier</subject><subject>Blood-Brain Barrier - cytology</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Blood-Brain Barrier - pathology</subject><subject>Brain</subject><subject>Brain - blood supply</subject><subject>Brain - cytology</subject><subject>Brain - metabolism</subject><subject>Carbon dioxide</subject><subject>Carbon dioxide removal</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Central nervous system</subject><subject>Cerebrovascular Circulation</subject><subject>Drug screening</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Homeostasis</subject><subject>Human influences</subject><subject>Humans</subject><subject>Immune clearance</subject><subject>Immune system</subject><subject>Immunosuppressive agents</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Induced Pluripotent Stem Cells - pathology</subject><subject>Membrane permeability</subject><subject>Metabolites</subject><subject>Modelling</subject><subject>Models, Biological</subject><subject>Neurodegenerative Diseases - metabolism</subject><subject>Neurodegenerative Diseases - pathology</subject><subject>Neurological diseases</subject><subject>Neurotoxins</subject><subject>Nutrients</subject><subject>Older people</subject><subject>Parkinson's disease</subject><subject>Pathogens</subject><subject>Pathology</subject><subject>Permeability</subject><subject>Pluripotency</subject><subject>Potassium</subject><subject>Proteins</subject><subject>Review</subject><subject>Stem cells</subject><subject>Toxins</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVkctLw0AQxhdRbK3ePEvAq9F9ZrMXwaa-wBeoB0_LZjNpt6RJ3U0r_vdGWks9zTDz45uP-RA6JvicMYUv3HQWKCVcSoJ3UJ9wSmOME7m71ffQQQhTjCmjQu2jHuNUKUbTPvoYVk1TxENvXB0NjfcOfGTqInqChW8KGEMN3rRuCdHIBTABQvzYzStXj6Mv104i9_KaxSPwHVJEK50Mqiocor3SVAGO1nWA3m-u37K7-OH59j67eogtJ7SNS2KVIGUp8oIlpMDM4JyklCvLKTeyVMpKboCnxia5IpbmhCaJFKXlSQ6pZAN0udKdL_IZFBbq1ptKz72bGf-tG-P0_03tJnrcLHXKsBSp6ARO1wK--VxAaPW0Wfi686ypEFwkKUtxR52tKOubEDyUmwsE698g9HYQHX6y7WoD_32e_QBVM4TI</recordid><startdate>20210719</startdate><enddate>20210719</enddate><creator>Wu, Ying-Chieh</creator><creator>Sonninen, Tuuli-Maria</creator><creator>Peltonen, Sanni</creator><creator>Koistinaho, Jari</creator><creator>Lehtonen, Šárka</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1817-1217</orcidid><orcidid>https://orcid.org/0000-0002-5055-9414</orcidid></search><sort><creationdate>20210719</creationdate><title>Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells</title><author>Wu, Ying-Chieh ; Sonninen, Tuuli-Maria ; Peltonen, Sanni ; Koistinaho, Jari ; Lehtonen, Šárka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-f1c951ff5bd361d03a0b18249c424a7f99c74ae48ac6b91c2b126675fc46be873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>Blood-brain barrier</topic><topic>Blood-Brain Barrier - cytology</topic><topic>Blood-Brain Barrier - metabolism</topic><topic>Blood-Brain Barrier - pathology</topic><topic>Brain</topic><topic>Brain - blood supply</topic><topic>Brain - cytology</topic><topic>Brain - metabolism</topic><topic>Carbon dioxide</topic><topic>Carbon dioxide removal</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Central nervous system</topic><topic>Cerebrovascular Circulation</topic><topic>Drug screening</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Homeostasis</topic><topic>Human influences</topic><topic>Humans</topic><topic>Immune clearance</topic><topic>Immune system</topic><topic>Immunosuppressive agents</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Induced Pluripotent Stem Cells - pathology</topic><topic>Membrane permeability</topic><topic>Metabolites</topic><topic>Modelling</topic><topic>Models, Biological</topic><topic>Neurodegenerative Diseases - metabolism</topic><topic>Neurodegenerative Diseases - pathology</topic><topic>Neurological diseases</topic><topic>Neurotoxins</topic><topic>Nutrients</topic><topic>Older people</topic><topic>Parkinson's disease</topic><topic>Pathogens</topic><topic>Pathology</topic><topic>Permeability</topic><topic>Pluripotency</topic><topic>Potassium</topic><topic>Proteins</topic><topic>Review</topic><topic>Stem cells</topic><topic>Toxins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Ying-Chieh</creatorcontrib><creatorcontrib>Sonninen, Tuuli-Maria</creatorcontrib><creatorcontrib>Peltonen, Sanni</creatorcontrib><creatorcontrib>Koistinaho, Jari</creatorcontrib><creatorcontrib>Lehtonen, Šárka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Ying-Chieh</au><au>Sonninen, Tuuli-Maria</au><au>Peltonen, Sanni</au><au>Koistinaho, Jari</au><au>Lehtonen, Šárka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2021-07-19</date><risdate>2021</risdate><volume>22</volume><issue>14</issue><spage>7710</spage><pages>7710-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer's disease and Parkinson's disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. 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| subjects | Alzheimer's disease Animals Blood-brain barrier Blood-Brain Barrier - cytology Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology Brain Brain - blood supply Brain - cytology Brain - metabolism Carbon dioxide Carbon dioxide removal Cell culture Cell cycle Central nervous system Cerebrovascular Circulation Drug screening Gene expression Growth factors Homeostasis Human influences Humans Immune clearance Immune system Immunosuppressive agents Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - pathology Membrane permeability Metabolites Modelling Models, Biological Neurodegenerative Diseases - metabolism Neurodegenerative Diseases - pathology Neurological diseases Neurotoxins Nutrients Older people Parkinson's disease Pathogens Pathology Permeability Pluripotency Potassium Proteins Review Stem cells Toxins |
| title | Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells |
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