Immortalized Blood Brain Barrier (BBB) Modeling Service

The blood-brain barrier (BBB) serves as a crucial interface between the bloodstream and the central nervous system (CNS). This barrier is primarily formed by specialized brain microvascular endothelial cells (BMECs) and is supported by various cell types within the neurovascular unit (NVU), including pericytes, astrocytes, and neurons. The BBB is vital for maintaining CNS homeostasis and plays significant roles in nutrient uptake, waste clearance, and the regulation of the brain's extracellular environment. Nevertheless, its selective permeability can pose significant challenges when it comes to drug delivery, as many therapeutic compounds struggle to penetrate this barrier effectively. This limitation can reduce the efficacy of treatments aimed at neurological conditions and underscores a major hurdle in the development of CNS-targeted therapies.

Creative Biolabs is committed to help scientists to assess the permeability of compounds, antibodies and adeno-associated virus across the BBB using in vitro BBB model.

Popular In Vitro BBB Model Models

The following BBB cell line models are widely used for research:

Human-derived BBB Models

• Immortalized Human Brain Microvascular Endothelial Cell Line hCMEC/D3
• Immortalized Human Brain Pericytes from Creative Biolabs
• Immortalized Human Astrocytes from Creative Biolabs
• Human Neuroblastoma SH-SY5Y Cell Line

Mouse-derived BBB Models

• Mouse Brain Microvascular Endothelial Cell Line (bEnd.3)
• Mouse Astrocyte Type III CD-830
• Immortalized Mouse Brain Pericytes from Creative Biolabs
• Immortalized Mouse Astrocytes from Creative Biolabs

Rat-derived BBB Models

• Immortalized Rat Brain Microvascular Endothelial Cells from Creative Biolabs
• Immortalized Rat Brain Pericytes from Creative Biolabs
• Immortalized Rat Astrocytes from Creative Biolabs

Applications

• Drug Screening and Development
  Screening compounds
  Toxicity testing
• Disease modeling
  Neurodegenerative diseases
  Ischemic stroke
  Infectious diseases
  Brain cancers

Case Study

The hCMEC/D3 cell line is derived from human cerebral microvascular endothelial cells by introducing the catalytic subunit of telomerase (hTERT) and the SV40 large T antigen via a highly effective lentiviral vector system. It is widely used in the study of BBB.

To investigate the role of 5-Hydroxytryptamine Receptor Type 4 (5-HT4) in BBB permeability, researchers characterized the serotonin receptor 5-HT4 in human brain slices and the hCMEC/D3 cell line. Additionally, they examined the effects of the 5-HT4 receptor agonist Prucalopride on the permeability of an in vitro BBB model using hCMEC/D3 cells.

Fig. 1 RT-qPCR (a), WB (b), and IF (c) analysis revealed the expression of the 5-HT4 receptor in the hCMEC/D3 cells.¹

Fig. 2 TEER assay showed the effects of Prucalopride (5-HT4 receptor agonist) and GR113808 (5-HT4 receptor antagonist) on permeability in hCMEC/D3 cells.¹

Fig. 3 WB results indicate that the 5-HT4 receptor plays a role in modulating the expression levels of tight junction proteins in hCMEC/D3 cells.¹

Reference

1. Becker, Guillaume et al. "Blood-Brain Barrier Permeability: Is 5-Hydroxytryptamine Receptor Type 4 a Game Changer?." Pharmaceutics. 2021;13(11):1856. Distributed under Open Access license CC BY 4.0 without modification.