Methods to assess pericyte-endothelial cell interactions in a coculture model
Gokulan Thanabalasundaram1, Jehad El-Gindi, Mira Lischper
1Institute of Biochemistry, Westfälische Wilhelms Universität Münster, Münster, Germany.
Methods in Molecular Biology (Clifton, N.J.)
|November 18, 2010
Summary
This study introduces a new coculture model to investigate the blood-brain barrier (BBB). The model explores the crucial role of pericytes and extracellular matrix interactions in BBB regulation and function.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- The blood-brain barrier (BBB) is crucial for brain homeostasis, composed of endothelial cells, pericytes, and astrocytes linked by extracellular matrix (ECM).
- Existing BBB models often neglect the significant role of pericytes in barrier regulation, focusing primarily on endothelial cells and their tight junctions (TJs).
- Pericyte-endothelial cell interactions, modulated by ECM remodeling via matrix metalloproteinases (MMPs), are vital for BBB integrity and function.
Purpose of the Study:
- To establish and validate a novel coculture model of primary porcine brain capillary endothelial cells (PBCECs) and pericytes (PBCPs).
- To investigate the impact of pericytes on the pharmacological, transport, migration, and metabolic activities of the BBB.
- To explore the mechanisms of cell-cell interaction through ECM signaling and MMP secretion.
Main Methods:
- Development of a coculture system using primary porcine brain capillary endothelial cells (PBCECs) and pericytes (PBCPs).
- In vitro assessment of BBB functions including transport, migration, and metabolic activity within the coculture model.
- Analysis of extracellular matrix (ECM) remodeling and matrix metalloproteinase (MMP) secretion by both cell types.
Main Results:
- The coculture model effectively mimics in vivo conditions, allowing for the study of pericyte influence on BBB properties.
- Demonstrated that pericytes significantly impact BBB functions beyond endothelial cell-mediated barrier formation.
- Identified the role of MMPs secreted by both endothelial cells and pericytes in ECM remodeling and TJ modulation.
Conclusions:
- The established PBCEC-PBCP coculture model provides a valuable platform for studying BBB physiology and pericyte contributions.
- Pericytes play a critical, yet underappreciated, role in regulating BBB function and integrity.
- Understanding ECM-MMP interactions is key to deciphering pericyte-endothelial cell communication within the BBB.
