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 – <
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.