The Microvascular Gap Junction Channel: A Route to Deliver MicroRNAs for Neurological Disease Treatment

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.

The Roles of miRNA in Glioblastoma Tumor Cell Communication: Diplomatic and Aggressive Negotiations

“…Since carbenoxolone inhibited the transfer of both miRNAs, it is highly likely that they use the same GJIC pathway to accomplish their transfer. Moreover, GJIC between GBM cells and HMECs lose their functionality in vitro after a few days; however, miR-5096 still manages to pass in a less efficient manner, probably through exosome release [69,93,94].…”

Non-Coding RNAs in Glioma Microenvironment and Angiogenesis

“…It has been demonstrated that miR-145-5p expressed in HMEC and miR-5096 derived from GBM cells can transfer between the two types of cells through GJIC. MiR-5096 may promote GBM invasiveness and angiogenesis after transferring into HMEC, while miR-145-5p acts as a tumor suppressor after moving into GBM cells (Thuringer et al, 2017 ). Direct cell-to-cell communication via GJIC is superior to indirect communication in terms of specificity and efficiency.…”

The Application Progress of MicroRNA in Cerebral Ischemia-reperfusion Injury

“…As mentioned above, miRNAs are related to the mechanisms of I/R, which has opened new fields of research for not only biomarkers, but also therapeutics of ischemic diseases. And iPSC (inducible pluripotent stem cells) derived BMEC (brain microvascular endothelial cells) have been designed to transfer miRNAs over the years, overcome the difficulty of crossing the blood brain barrier [16] ,locked nucleic acid (LNA) and chemically modified miRNAs vectors overcome the stability of miRNAs in vivo, make it possible for miRNAs based gene therapy to cure I/R. Yet, miRNAs treatment is far from safe and effective clinical application.…”