Conditionally immortalized syncytiotrophoblast cell lines as new tools for study of the blood-placenta barrier.
Syncytiotrophoblasts play an essential role in restriction of drug delivery through the blood-placenta barrier (BPB). Conditionally immortalized syncytiotrophoblast cell lines, TR-TBTs, were established at gestational day 18 from pregnant transgenic rats (Tg-rats) harboring the temperature-sensitive SV 40 (ts SV40) large T-antigen. TR-TBTs exhibit temperature-sensitive cell growth due to the expression of SV 40 large T-antigen, and thus the cell growth can be regulated by changing the culture temperature. TR-TBTs exhibit typical properties of syncytiotrophoblast cells, such as syncytium-like morphology, the expression of cytokeratins and hormones, and polarized expression of glucose transporter 1 (GLUT1) and GLUT3. TR-TBTs express in vivo influx and efflux transporters, such as taurine transporter (TauT), betaine/GABA transporter (BGT-1), amino acid transporter 2 (ATA2), organic anion transporting polypeptide 2 (oatp2), organic cation/carnitine transporter (OCTN2), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP/ABCG2). Moreover, TR-TBTs exhibit taurine, GABA, and DHEA-S uptake activity via TauT, BGT-1, and oatp2, respectively. Therefore, TR-TBTs can be used for the analysis of these functions and would be a good in vitro models for investigating carrier-mediated transport functions at the BPB.
Kitano
Tomohide
T
Department of Pharmaceutics, Kyoritsu University of Pharmacy, Tokyo, Japan.
Iizasa
Hisashi
H
Hwang
In-Won
IW
Hirose
Yoko
Y
Morita
Tomonari
T
Maeda
Tomomi
T
Nakashima
Emi
E
D000818:Animals; D002461:Cell Line, Transformed; D005260:Female; D006801:Humans; D010920:Placenta / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D021041:Placental Circulation / Q000502:physiology*; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*