UW-Madison researchers have developed a method for differentiation of human pluripotent stem cells (hPSCs) into endothelial cells (ECs) resulting in a model having improved fidelity to BBB gene expression and function. During the differentiation, cell populations are treated with a small molecule along with overexpression of one or a combination of key BBB transcription factors (TFs. Overexpression of one or a combination of these transcription factors induces global transcriptomic similarity to in vivo BBB ECs, including changes that reflect key BBB properties. These include increased tight junction protein expression, increased transporter protein expression, reduced transcytosis-related protein expression, and reduced leukocyte adhesion molecule expression. To date, no existing human endothelial cell model has demonstrated such accurate recapitulation of BBB phenotypes.
This innovation could be utilized for BBB permeability screening for small molecule drugs, biologics, viral vectors, and cells, as well as research on BBB development and dysfunction in health and disease. Eventually, this innovation could be used for patient-specific and disease-specific modeling of human neurological diseases at the BBB, enabling personalized treatment strategies.