Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood-Brain Barrier System

Dianjun Qi, Shaohua Wu, Haishuang Lin, Mitchell A. Kuss, Yuguo Lei, Alexey V Krasnoslobodtsev, Shaheen Ahmed, Chi Zhang, Hyung Joon Kim, Peng Jiang, Bin Duan

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21825-21835
Number of pages11
JournalACS Applied Materials and Interfaces
Volume10
Issue number26
DOIs
StatePublished - Jul 5 2018

Fingerprint

Nanofibers
Tight Junction Proteins
Brain
Acoustic impedance
Endothelial cells
Physiology
Pathology
Proteins
Membranes
Biopolymers
Diffusion barriers
Acids
Blood-Brain Barrier
Poisons
Pathogens
Paclitaxel
Stem cells
Fluorescein
Drug delivery
Amyloid

Keywords

  • 3D printing
  • drug screening
  • electrospinning
  • human induced pluripotent stem cells
  • transepithelial electrical resistance

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood-Brain Barrier System. / Qi, Dianjun; Wu, Shaohua; Lin, Haishuang; Kuss, Mitchell A.; Lei, Yuguo; Krasnoslobodtsev, Alexey V; Ahmed, Shaheen; Zhang, Chi; Kim, Hyung Joon; Jiang, Peng; Duan, Bin.

In: ACS Applied Materials and Interfaces, Vol. 10, No. 26, 05.07.2018, p. 21825-21835.

Research output: Contribution to journalArticle

Qi, Dianjun ; Wu, Shaohua ; Lin, Haishuang ; Kuss, Mitchell A. ; Lei, Yuguo ; Krasnoslobodtsev, Alexey V ; Ahmed, Shaheen ; Zhang, Chi ; Kim, Hyung Joon ; Jiang, Peng ; Duan, Bin. / Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood-Brain Barrier System. In: ACS Applied Materials and Interfaces. 2018 ; Vol. 10, No. 26. pp. 21825-21835.
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