Placenta-derived extracellular vesicles: their unique characteristics of the blood-brain barrier transport  

Masanori Tachikawa 1 , Mai Inagaki 1 , Hinori Sano 2 , Momoko Sato 2 , Hidetaka Kosako 3 , Kenichi Funamoto 4  

1 Graduate  School  of  Biomedical  Sciences; 
2 Graduate  School  of  Pharmaceutical  Sciences;
3 Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan; 
4 Institute of Fluid Science, Tohoku University, Sendai, Japan  

Correspondence: Masanori Tachikawa – <This email address is being protected from spambots. You need JavaScript enabled to view it.>  

The placenta,  an organ specific for pregnant women, secrets  the unique nano-size particles which we call placenta-derived extracellular vesicles (pEVs). The pEVs encapsulate nucleic acid,  e.g.,  miRNA,  and  functional  proteins  as  message  substances  and  play  a  role  in  the placenta-to-maternal  organs  signal  transductions.  An  interesting  report  has  shown  that pregnancy causes a reduction in the brain gray matter region subserving social cognition (Nat Neurosci  20:287-296,  2017).  This  implies  that  pEVs  could  mediate  the  placenta-to-brain delivery of the message substances such as miRNA beyond the blood-brain barrier (BBB). In support of this notion, we found that the placenta-related miRNAs are present in the pregnant mouse brain as well  as in blood-circulating extracellular vesicles. Thus,  the purpose of  the present study was to clarify the pEVs transport at the BBB. The pEVs were obtained from the human placental trophoblast cells (BeWo cells) by ultracentrifugation. The three-dimensional human brain microvasculature model was our originally constructed on a microfluidic device. We succeeded in visualizing the pEVs which were transported to the brain parenchymal cells across the brain microvasculature on a microfluidic device. We also identified the virus receptor as the potent transport system of pEVs at the BBB by proteomics- and gene knockout-based studies. In this symposium, I will introduce our recent data on the uniqueness of pEVs and the transport characteristics of pEVs at the BBB, which have been clarified by human BBB on-a-chip and proteomics. I will also propose a concept of pEVs-mediated placenta-to-brain signal transduction via the BBB.