Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood–Brain Barrier System
Open accessAbstract
The blood-brain barrier (BBB) is an active and complex diffusion barrier that separates the circulating blood from the brain and extracellular fluid, regulates nutrient transportation, and provides protection against various toxic compounds and pathogens. Creating an in vitro microphysiological BBB system, particularly with relevant human cell types, will significantly facilitate the research of neuropharmaceutical drug delivery, screening, and transport, as well as improve our understanding of pathologies that are due to BBB damage. Currently, most of the in vitro BBB models are generated by culturing rodent astrocytes and endothelial cells, using commercially available transwell membranes. Those membranes are made of plastic biopolymers that are nonbiodegradable, porous, and stiff. In addition, distinct from rodent astrocytes, human astrocytes possess unique cell complexity and physiology, which are among the few characteristics that differentiate human brains from rodent brains. In this study, we established a novel human BBB microphysiologocal system, consisting of a three-dimensionally printed holder with a electrospun poly(lactic- co-glycolic) acid (PLGA) nanofibrous mesh, a bilayer coculture of human astrocytes, and endothelial cells, derived from human induced pluripotent stem cells (hiPSCs), on the electrospun PLGA mesh. This human BBB model achieved significant barrier integrity with tight junction protein expression, an effective permeability to sodium fluorescein, and higher transendothelial electrical resistance (TEER) comparing to electrospun mesh-based counterparts. Moreover, the coculture of hiPSC-derived astrocytes and endothielial cells promoted the tight junction protein expression and the TEER value. We further verified the barrier functions of our BBB model with antibrain tumor drugs (paclitaxel and bortezomib) and a neurotoxic peptide (amyloid β 1-42). The human microphysiological system generated in this study will potentially provide a new, powerful tool for research on human BBB physiology and pathology.
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Manipulating synthetic hydrogels using methods such as electrospinning, photopatterning, spraying of microspheres, inkjet and 3D printing, or microfluidic channels enables control over the shape and size of the organoids.
“Manipulating synthetic hydrogels using methods such as electrospinning125, photopatterning126,127, spraying of microspheres128, inkjet and 3D printing129, or microfluidic channels130 further enables control over the shape and size of the organoids.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [125]
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Research works printed but not linked: 1
- [66]Chen W Chan Y Wan W Li Y Zhang C Abeta1–42 Induces Cell Damage via RAGE-Dependent Endoplasmic Reticulum Stress in bEnd.3 cells Exp. Cell Res 2017 362 83 29154819
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Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works
- Authors
- Qi, D., Wu, S., Lin, H., Kuss, M. A., Lei, Y., Krasnoslobodtsev, A., Ahmed, S., Zhang, C., Kim, H. J., Jiang, P., & Duan, B.
- Affiliations
- First Hospital of China Medical University (CN)
- Qingdao University (CN)
- University of Nebraska–Lincoln (US)
- University of Nebraska Medical Center (US)
- University of Nebraska at Omaha (US)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Jiang, Peng
- Duan, Bin
- ORCID
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-06-13
- Volume
- 10
- Issue
- 26
- Pages
- 21825-21835
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- PMC
- PMC6052796
- OpenAlex
- W2808278622
- Cited by
- 62
- References
- 69
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 11 · 2021: 11 · 2020: 8 · 2019: 9 · 2018: 1
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS102382)
- Nebraska Department of Health and Human Services
- National Institute of Child Health and Human Development (R21HD091512)
- University of Nebraska Medical Center
- State of Nebraska
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- blood-brain barrier, human induced pluripotent stem cells, microphysiological systems, human astrocytes, endothelial cells, tight junction proteins, transendothelial electrical resistance, drug permeability, amyloid-beta 42, paclitaxel, bortezomib
- MeSH terms
- Astrocytes, Blood-Brain Barrier, Cells, Cultured, Humans, Amyloid beta-Peptides, Coculture Techniques, Induced Pluripotent Stem Cells, Nanofibers
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