Abstract
Brain microvascular endothelial cells (BMECs) separate the peripheral blood from the brain. These cells, which are surrounded by basal lamina, pericytes and glial cells, are highly interconnected through tight and gap junctions. Their permeability properties restrict the transfer of potentially useful therapeutic agents. In such a hermetic system, the gap junctional exchange of small molecules between cerebral endothelial and non-endothelial cells is crucial for maintaining tissue homeostasis. MicroRNA were shown to cross gap junction channels, thereby modulating gene expression and function of the recipient cell. It was also shown that, when altered, BMEC could be regenerated by endothelial cells derived from pluripotent stem cells. Here, we discuss the transfer of microRNA through gap junctions between BMEC, the regeneration of BMEC from induced pluripotent stem cells that could be engineered to express specific microRNA, and how such an innovative approach could benefit to the treatment of glioblastoma and other neurological diseases.
Highlights
Human brain microvascular endothelial cells (BMECs) interact with astrocytes and pericytes to form a functional “neurovascular unit” called the blood–brain barrier (BBB), which protects the central nervous system by preventing the transfer of circulating molecules from the bloodstream to the brain parenchyma
Microvascular endothelial cells derived from induced pluripotent stem cells were used to further explore BBB development and maintenance by co-culture with neural cells
Adhesion of cells to an endothelial monolayer is usually achieved in less than 1 h, cell–cell communication is established in 1–2 h and the gap junctional shuttling of microRNA observed within 3 h in vitro (Thuringer et al, 2015b, 2016a)
Summary
Human brain microvascular endothelial cells (BMECs) interact with astrocytes and pericytes to form a functional “neurovascular unit” called the blood–brain barrier (BBB), which protects the central nervous system by preventing the transfer of circulating molecules from the bloodstream to the brain parenchyma. Microvascular endothelial cells derived from induced pluripotent stem cells (iPSC) were used to further explore BBB development and maintenance by co-culture with neural cells. These iPSC appeared as a biological tools to screen neuropharmaceuticals (Lippmann et al, 2013, 2014a; Cecchelli et al, 2014; Minami et al, 2015; Katt et al, 2016; Appelt-Menzel et al, 2017; Yamamizu et al, 2017). Analysis of gap junction channels between heterotypic cells suggested promising applications by blocking or promoting microRNA transfer and delivery (Valiunas et al, 2005; Lemcke et al, 2015)
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