The blood-brain barrier (BBB) is established by specialized microvascular endothelial cells the brain and spinal cord, which form a tight barrier. However, barrier properties of the BBB endothelial cells are not intrinsic and rather rely on the continuous crosstalk with additional cells of the neurovascular unit, namely pericytes and astrocytes. We have proposed that BBB dysfunction contributes to the pathogenesis of multiple sclerosis (MS). Yet, the contribution of the pericytes in BBB dysfunction in MS is not understood.

To this end, we make use of a human induced pluripotent stem cell (hiPSC)-derived in vitro model of the neurovascular unit composed of extended endothelial cell culture differentiated brain microvascular endothelial cells (EECM-BMECs) and brain pericyte like cells (BPLC) to ultimately understand the potential role of pericyte-induced crosstalk in BBB dysfunction in MS.

We first assessed the effect of conditioned media obtained from healthy control (HC)-derived BPLCs the immune phenotype of HC-derived EECM-BMECs. When stimulated with HC-derived BPLC conditioned media and pro-inflammatory cytokines, EECM-BMECs had an increased protein expression of ICAM-1 and VCAM-1 compared to stimulation with pro-inflammatory cytokines only. This result underlines that BPLC may have a paracrine effect on the immune phenotype of EECM-BMECs. Thus, we have next analyzed the secretome of HC- and MS-derived BPLCs and are currently testing the effect of the identified pericyte-derived modulators on EECM-BMECs phenotype and barrier function.

Investigating the composition and function of the secretome of MS-derived BPLCs will then allow to determine the molecular underpinnings of the of the potential disturbances in the cellular crosstalk of pericytes with BBB endothelial cells in MS.