Human‐Based<i>In Vitro</i>Brain Endothelial Cell Models

Wilson, Hannah K.; Shusta, Eric V.

doi:10.1002/9781118788523.ch11

Cited by 3 publications

(1 citation statement)

References 218 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, other immortalized human BBB models, such as the human cerebral microvascular endothelial cell (hCMEC) line hCMEC/D3, have been developed. In contrast to the immortalized hBMECs described here, hCMEC/D3s do express junctional claudin-5; however, occludin expression is discontinuous, leading to modest TEERs (~40 Ω × cm 2 ) that are not substantially improved upon coculture with astrocytes ( 35 , 36 , 53 – 56 ). Similar to immortalized human BMEC lines, the iPSC-derived BMEC model offers a reliable and scalable method of generating BMECs that express BBB markers.…”

Section: Discussioncontrasting

confidence: 64%

Modeling Group BStreptococcusand Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

Kim

Bee

McDonagh

et al. 2017

mSphere

Self Cite

View full text Add to dashboard Cite

Here for the first time, human iPSC-derived BMECs were used to model bacterial interaction with the BBB. Unlike models previously used to study these interactions, iPSC-derived BMECs possess robust BBB properties, such as the expression of complex tight junctions that are key components for the investigation of bacterial effects on the BBB. Here, we demonstrated that GBS interacts with the iPSC-derived BMECs and specifically disrupts these tight junctions. Thus, using this BBB model may allow researchers to uncover novel mechanisms of BBB disruption during meningitis that are inaccessible to immortalized or primary cell models that lack substantial tight junctions.

show abstract

Section: Discussioncontrasting

confidence: 64%

Modeling Group BStreptococcusand Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

Kim

Bee

McDonagh

et al. 2017

mSphere

Self Cite

View full text Add to dashboard Cite

show abstract

Blood-Brain Barrier Methods

Kerns¹,

Di²

2016

Drug-Like Properties

View full text Add to dashboard Cite

Inhibition of radiation-induced glioblastoma invasion by genetic and pharmacological targeting of MDA-9/Syntenin

Kegelman

Das

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

130

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is an intractable tumor despite therapeutic advances, principally because of its invasive properties. Radiation is a staple in therapeutic regimens, although cells surviving radiation can become more aggressive and invasive. Subtraction hybridization identified melanoma differentiation-associated gene 9 [MDA-9/Syntenin; syndecan-binding protein (SDCBP)] as a differentially regulated gene associated with aggressive cancer phenotypes in melanoma. MDA-9/Syntenin, a highly conserved double-PDZ domain-containing scaffolding protein, is robustly expressed in human-derived GBM cell lines and patient samples, with expression increasing with tumor grade and correlating with shorter survival times and poorer response to radiotherapy. Knockdown of MDA-9/Syntenin sensitizes GBM cells to radiation, reducing postradiation invasion gains. Radiation induces Src and EGFRvIII signaling, which is abrogated through MDA-9/Syntenin down-regulation. A specific inhibitor of MDA-9/Syntenin activity, PDZ1i (113B7), identified through NMR-guided fragment-based drug design, inhibited MDA-9/Syntenin binding to EGFRvIII, which increased following radiation. Both genetic (shmda-9) and pharmacological (PDZ1i) targeting of MDA-9/Syntenin reduced invasion gains in GBM cells following radiation. Although not affecting normal astrocyte survival when combined with radiation, PDZ1i radiosensitized GBM cells. PDZ1i inhibited crucial GBM signaling involving FAK and mutant EGFR, EGFRvIII, and abrogated gains in secreted proteases, MMP-2 and MMP-9, following radiation. In an in vivo glioma model, PDZ1i resulted in smaller, less invasive tumors and enhanced survival. When combined with radiation, survival gains exceeded radiotherapy alone. MDA-9/Syntenin (SDCBP) provides a direct target for therapy of aggressive cancers such as GBM, and defined small-molecule inhibitors such as PDZ1i hold promise to advance targeted brain cancer therapy.

show abstract

Human‐BasedIn VitroBrain Endothelial Cell Models

Cited by 3 publications

References 218 publications

Modeling Group BStreptococcusand Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

Modeling Group BStreptococcusand Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

Blood-Brain Barrier Methods

Inhibition of radiation-induced glioblastoma invasion by genetic and pharmacological targeting of MDA-9/Syntenin

Contact Info

Product

Resources

About