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A novel human induced pluripotent stem cell blood-brain barrier model: Applicability to study antibody-triggered receptor-mediated transcytosis.
Ribecco-Lutkiewicz, Maria; Sodja, Caroline; Haukenfrers, Julie; Haqqani, Arsalan S; Ly, Dao; Zachar, Peter; Baumann, Ewa; Ball, Marguerite; Huang, Jez; Rukhlova, Marina; Martina, Marzia; Liu, Qing; Stanimirovic, Danica; Jezierski, Anna; Bani-Yaghoub, Mahmud.
Affiliation
  • Ribecco-Lutkiewicz M; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Sodja C; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Haukenfrers J; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Haqqani AS; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Ly D; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Zachar P; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Baumann E; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Ball M; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Huang J; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Rukhlova M; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Martina M; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Liu Q; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Stanimirovic D; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
  • Jezierski A; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada. anna.jezierski@nrc.ca.
  • Bani-Yaghoub M; Human Health Therapeutics Portfolio, National Research Council of Canada, Ottawa, ON, K1A 0R6, Canada.
Sci Rep ; 8(1): 1873, 2018 01 30.
Article in En | MEDLINE | ID: mdl-29382846
ABSTRACT
We have developed a renewable, scalable and transgene free human blood-brain barrier model, composed of brain endothelial cells (BECs), generated from human amniotic fluid derived induced pluripotent stem cells (AF-iPSC), which can also give rise to syngeneic neural cells of the neurovascular unit. These AF-iPSC-derived BECs (i-BEC) exhibited high transendothelial electrical resistance (up to 1500 Ω cm2) inducible by astrocyte-derived molecular cues and retinoic acid treatment, polarized expression of functional efflux transporters and receptor mediated transcytosis triggered by antibodies against specific receptors. In vitro human BBB models enable pre-clinical screening of central nervous system (CNS)-targeting drugs and are of particular importance for assessing species-specific/selective transport mechanisms. This i-BEC human BBB model discriminates species-selective antibody- mediated transcytosis mechanisms, is predictive of in vivo CNS exposure of rodent cross-reactive antibodies and can be implemented into pre-clinical CNS drug discovery and development processes.
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Full text: 1 Database: MEDLINE Main subject: Brain / Blood-Brain Barrier / Cell Differentiation / Receptors, Cell Surface / Induced Pluripotent Stem Cells / Transcytosis / Antibodies Type of study: Prognostic_studies Limits: Animals / Humans / Male Language: En Year: 2018 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Brain / Blood-Brain Barrier / Cell Differentiation / Receptors, Cell Surface / Induced Pluripotent Stem Cells / Transcytosis / Antibodies Type of study: Prognostic_studies Limits: Animals / Humans / Male Language: En Year: 2018 Type: Article