Concerns Raised Over Protocols Used to Generate iBMECs

Cells used to study the human blood brain barrier in the lab aren't what they seem, according to a new study from scientists at Columbia University who recently completed a comprehensive transcriptomic metaanalysis of human PSC-derived iBMECs.

The team also discovered a possible way to correct the error, raising hopes of creating a more accurate model of the human blood-brain barrier for studying certain neurological diseases and developing drugs that can cross it.

The team’s analysis revealed that the supposed human brain endothelial cells were missing several key proteins found in natural endothelial cells and had more in common with a completely different type of cell (epithelial) that is normally not found in the brain.

The team also identified three genes that, when activated within induced pluripotent cells, lead to the creation of cells that behave more like bona fide endothelial cells. More work is still needed, Dritan Agalliu, co-study leader of the paper published in Proceedings of the National Academy of Sciences (PNAS) last week, says, to create endothelial cells that produce a reliable model of the human blood-brain barrier.

"The misidentification of human brain endothelial cells may be an issue for other types of cells made from induced pluripotent cells such as astrocytes or pericytes that form the neurovascular unit," Agalliu explains. The protocols to generate these cells were created before the advent of single-cell technologies that are better at uncovering a cell's identity. "Cell misidentification remains a major problem that needs to be addressed in the scientific community in order to develop cells that mirror those found in the human brain. This will allow us to use these cells to study the role of genetic risk factors for neurological disorders and develop drug therapies that target the correct cells that contribute to the blood-brain barrier."