Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System
The blood-brain barrier (BBB) is responsible for the homeostasis between the cerebral vasculature and the brain and it has a key role in regulating the influx and efflux of substances, in healthy and diseased states. Stem cell technology offers the opportunity to use human brain-specific cells to es...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/994 |
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| author | Annalise Di Marco Domenico Vignone Odalys Gonzalez Paz Ivan Fini Maria Rosaria Battista Antonella Cellucci Elena Bracacel Giulio Auciello Maria Veneziano Vinod Khetarpal Mark Rose Alessandro Rosa Isabelle Gloaguen Edith Monteagudo Todd Herbst Celia Dominguez Ignacio Muñoz-Sanjuán |
| author_facet | Annalise Di Marco Domenico Vignone Odalys Gonzalez Paz Ivan Fini Maria Rosaria Battista Antonella Cellucci Elena Bracacel Giulio Auciello Maria Veneziano Vinod Khetarpal Mark Rose Alessandro Rosa Isabelle Gloaguen Edith Monteagudo Todd Herbst Celia Dominguez Ignacio Muñoz-Sanjuán |
| author_sort | Annalise Di Marco |
| collection | DOAJ |
| description | The blood-brain barrier (BBB) is responsible for the homeostasis between the cerebral vasculature and the brain and it has a key role in regulating the influx and efflux of substances, in healthy and diseased states. Stem cell technology offers the opportunity to use human brain-specific cells to establish in vitro BBB models. Here, we describe the establishment of a human BBB model in a two-dimensional monolayer culture, derived from human induced pluripotent stem cells (hiPSCs). This model was characterized by a transendothelial electrical resistance (TEER) higher than 2000 Ω∙cm<sup>2</sup> and associated with negligible paracellular transport. The hiPSC-derived BBB model maintained the functionality of major endothelial transporter proteins and receptors. Some proprietary molecules from our central nervous system (CNS) programs were evaluated revealing comparable permeability in the human model and in the model from primary porcine brain endothelial cells (PBECs). |
| first_indexed | 2024-03-10T20:26:31Z |
| format | Article |
| id | doaj.art-d4344a862cc142e2914339bfced09308 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:26:31Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d4344a862cc142e2914339bfced093082023-11-19T21:48:11ZengMDPI AGCells2073-44092020-04-019499410.3390/cells9040994Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based SystemAnnalise Di Marco0Domenico Vignone1Odalys Gonzalez Paz2Ivan Fini3Maria Rosaria Battista4Antonella Cellucci5Elena Bracacel6Giulio Auciello7Maria Veneziano8Vinod Khetarpal9Mark Rose10Alessandro Rosa11Isabelle Gloaguen12Edith Monteagudo13Todd Herbst14Celia Dominguez15Ignacio Muñoz-Sanjuán16High content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyHigh content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyHigh content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyHigh content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyHigh content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyHigh content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyDrug Metabolism and Pharmacokinetics, IRBM SpA, 00071 Pomezia, ItalyHigh content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyDrug Metabolism and Pharmacokinetics, IRBM SpA, 00071 Pomezia, ItalyCHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USACHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USADepartment of Biology and Biotechnology Charles Darwin, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, ItalyHigh content Biology and Screening, IRBM SpA, 00071 Pomezia, ItalyDrug Metabolism and Pharmacokinetics, IRBM SpA, 00071 Pomezia, ItalyCHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USACHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USACHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USAThe blood-brain barrier (BBB) is responsible for the homeostasis between the cerebral vasculature and the brain and it has a key role in regulating the influx and efflux of substances, in healthy and diseased states. Stem cell technology offers the opportunity to use human brain-specific cells to establish in vitro BBB models. Here, we describe the establishment of a human BBB model in a two-dimensional monolayer culture, derived from human induced pluripotent stem cells (hiPSCs). This model was characterized by a transendothelial electrical resistance (TEER) higher than 2000 Ω∙cm<sup>2</sup> and associated with negligible paracellular transport. The hiPSC-derived BBB model maintained the functionality of major endothelial transporter proteins and receptors. Some proprietary molecules from our central nervous system (CNS) programs were evaluated revealing comparable permeability in the human model and in the model from primary porcine brain endothelial cells (PBECs).https://www.mdpi.com/2073-4409/9/4/994blood brain barrierhuman induced pluripotent stem cellsCNSpermeabilityHuntington’s disease |
| spellingShingle | Annalise Di Marco Domenico Vignone Odalys Gonzalez Paz Ivan Fini Maria Rosaria Battista Antonella Cellucci Elena Bracacel Giulio Auciello Maria Veneziano Vinod Khetarpal Mark Rose Alessandro Rosa Isabelle Gloaguen Edith Monteagudo Todd Herbst Celia Dominguez Ignacio Muñoz-Sanjuán Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System Cells blood brain barrier human induced pluripotent stem cells CNS permeability Huntington’s disease |
| title | Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System |
| title_full | Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System |
| title_fullStr | Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System |
| title_full_unstemmed | Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System |
| title_short | Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System |
| title_sort | establishment of an in vitro human blood brain barrier model derived from induced pluripotent stem cells and comparison to a porcine cell based system |
| topic | blood brain barrier human induced pluripotent stem cells CNS permeability Huntington’s disease |
| url | https://www.mdpi.com/2073-4409/9/4/994 |
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