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  • Brain microvascular endothelial cells derived from human induced pluripotent stem cells as in vitro model for assessing blood-brain barrier transferrin receptor-mediated transcytosis.

Brain microvascular endothelial cells derived from human induced pluripotent stem cells as in vitro model for assessing blood-brain barrier transferrin receptor-mediated transcytosis.

Materials today. Bio (2022-03-22)
Marie Piantino, Fiona Louis, Yukari Shigemoto-Mogami, Kimiko Kitamura, Kaoru Sato, Tomoko Yamaguchi, Kenji Kawabata, Syunsuke Yamamoto, Shinji Iwasaki, Hideki Hirabayashi, Michiya Matsusaki
ABSTRACT

The blood-brain barrier (BBB), a selective barrier formed by brain microvascular endothelial cells (BMEC), represents a major challenge for the efficient accumulation of pharmaceutical drugs into the brain. The receptor-mediated transcytosis (RMT) has recently gained increasing interest for pharmaceutical industry as it shows a great potential to shuttle large-sized therapeutic cargos across the BBB. Confirming the presence of the RMT pathway by BMEC is therefore important for the screening of peptides or antibody libraries that bind RMT receptors. Herein, a comparative study was performed between a human cell line of BMEC (HBEC) and human induced pluripotent stem cells-derived BMEC-like cells (hiPS-BMEC). The significantly higher gene and protein expressions of transporters and tight junction proteins, excepting CD31 and VE-cadherin were exhibited by hiPS-BMEC than by HBEC, suggesting more biomimetic BBB features of hiPS-BMEC. The presence and functionality of transferrin receptor (TfR), known to use RMT pathway, were confirmed using hiPS-BMEC by competitive binding assays and confocal microscopy observations. Finally, cysteine-modified T7 and cysteine modified-Tfr-T12 peptides, previously reported to be ligands of TfR, were compared regarding their permeability using hiPS-BMEC. The hiPS-BMEC could be useful for the identification of therapeutics that can be transported across the BBB using RMT pathway.

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Human Serum, from platelet poor human plasma, sterile-filtered, (mycoplasma tested, virus tested)
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