Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development
Summary: Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microva...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-04-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671118301036 |
| _version_ | 1819076119053205504 |
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| author | Samuel Sances Ritchie Ho Gad Vatine Dylan West Alex Laperle Amanda Meyer Marlesa Godoy Paul S. Kay Berhan Mandefro Seigo Hatata Chris Hinojosa Norman Wen Dhruv Sareen Geraldine A. Hamilton Clive N. Svendsen |
| author_facet | Samuel Sances Ritchie Ho Gad Vatine Dylan West Alex Laperle Amanda Meyer Marlesa Godoy Paul S. Kay Berhan Mandefro Seigo Hatata Chris Hinojosa Norman Wen Dhruv Sareen Geraldine A. Hamilton Clive N. Svendsen |
| author_sort | Samuel Sances |
| collection | DOAJ |
| description | Summary: Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs) share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition. : Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development. Keywords: organ-on-chip, spinal cord, iPSC, disease modeling, amyotrophic lateral sclerosis, microphysiological system, brain microvascular endothelial cells, spinal motor neurons, vasculature, microfluidic device |
| first_indexed | 2024-12-21T18:36:14Z |
| format | Article |
| id | doaj.art-e1c4fcc300f543d9b59a13d1f73ed7bf |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-21T18:36:14Z |
| publishDate | 2018-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-e1c4fcc300f543d9b59a13d1f73ed7bf2022-12-21T18:54:08ZengElsevierStem Cell Reports2213-67112018-04-0110412221236Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal DevelopmentSamuel Sances0Ritchie Ho1Gad Vatine2Dylan West3Alex Laperle4Amanda Meyer5Marlesa Godoy6Paul S. Kay7Berhan Mandefro8Seigo Hatata9Chris Hinojosa10Norman Wen11Dhruv Sareen12Geraldine A. Hamilton13Clive N. Svendsen14Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Corresponding authorBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; iPSC Core, The David Janet Polak Foundation Stem Cell Core Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USAEmulate Inc., 27 Drydock Avenue, 5th Floor, Boston, MA 02210, USAEmulate Inc., 27 Drydock Avenue, 5th Floor, Boston, MA 02210, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; iPSC Core, The David Janet Polak Foundation Stem Cell Core Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAEmulate Inc., 27 Drydock Avenue, 5th Floor, Boston, MA 02210, USABoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA; Corresponding authorSummary: Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs) share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition. : Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development. Keywords: organ-on-chip, spinal cord, iPSC, disease modeling, amyotrophic lateral sclerosis, microphysiological system, brain microvascular endothelial cells, spinal motor neurons, vasculature, microfluidic devicehttp://www.sciencedirect.com/science/article/pii/S2213671118301036 |
| spellingShingle | Samuel Sances Ritchie Ho Gad Vatine Dylan West Alex Laperle Amanda Meyer Marlesa Godoy Paul S. Kay Berhan Mandefro Seigo Hatata Chris Hinojosa Norman Wen Dhruv Sareen Geraldine A. Hamilton Clive N. Svendsen Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development Stem Cell Reports |
| title | Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development |
| title_full | Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development |
| title_fullStr | Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development |
| title_full_unstemmed | Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development |
| title_short | Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development |
| title_sort | human ipsc derived endothelial cells and microengineered organ chip enhance neuronal development |
| url | http://www.sciencedirect.com/science/article/pii/S2213671118301036 |
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