Interstitial flow enhances the formation, connectivity, and function of 3D brain microvascular networks generated within a microfluidic device
| Autor: | Guohao Dai, Diana Y Kim, Nathaniel Silvia, Shravani Kakarla, Alexander Grath, Max A Winkelman |
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| Rok vydání: | 2021 |
| Předmět: |
Biomedical Engineering
Bioengineering Biochemistry Article Laminin Lab-On-A-Chip Devices medicine Humans Microvessel Barrier function Cells Cultured biology Chemistry Brain Endothelial Cells General Chemistry Human brain In vitro medicine.anatomical_structure Permeability (electromagnetism) Blood-Brain Barrier Microvessels Biophysics biology.protein Basal lamina Pericytes Astrocyte |
| Zdroj: | Lab Chip |
| ISSN: | 1473-0189 |
| Popis: | The convective transport of fluid through tissue is an important factor in human biology, including the development of brain microvascular networks (MVNs) with a functional blood-brain barrier (BBB). Engineering a functional 3D brain vascular network has great potential for modeling drug transport and neurovascular diseases. However, most in vitro models of brain MVNs do not utilize interstitial flow during the generation of microvessels. Using a microfluidic device (MFD), we cultured primary human brain endothelial cells (BECs), pericytes, and astrocytes within a 3D fibrin matrix under static and flow conditions. Interstitial flow was found to be beneficial for both angiogenic and vasculogenic microvessel formation. Only brain MVNs cultured under flow conditions achieved anastomosis and were perfusable, whereas those under static condition lacked connectivity and cannot be perfused. Compared to static culture, microvessels developed in flow culture exhibited enhanced microvessel area, branch length and diameter, connectivity, and longevity. Although there was no change in pericyte coverage of microvessels, a slight increase in astrocyte coverage was observed in the flow condition. In addition, the immunofluorescence intensity of basal lamina proteins, collagen IV and laminin, was nearly doubled in flow culture. Lastly, the barrier function of brain microvessels was enhanced under flow conditions, as demonstrated by decreased permeability to macromolecules. Taken together, these results highlighted the significance of interstitial flow in the generation of perfused brain MVNs and demonstrated the efficacy of MFDs to recapitulate the human BBB in vitro. |
| Databáze: | OpenAIRE |
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