SGLT1-mediated transport in Caco-2 cells is highly dependent on cell bank origin

B Steffansen, Maria Pedersen, A M Laghmoch, C U Nielsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The Caco-2 cell line is a well-established in vitro model for studying transport phenomena for prediction of intestinal nutrient and drug absorption. However, for substances depending on transporters such predictions are complicated due to variable transporter expression and limited knowledge about transporter function during multiple cell passaging and cell thawings. In the case of SGLT1, a key transporter of oral absorption of D-glucose, one reason for compromised prediction could be inadequate expression of SGLT1 in Caco-2 cells and thereby limited sensitivity in the determination of SGLT1-mediated permeability (PSGLT1). Here, the objective was to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate, α-MDG, in Caco-2 cells was shown to be highly dependent on cell bank origin. The most robust and reliable SGLT1 functionality was identified in Caco-2 cells from DSMZ, whereas cells from ATCC and ECACC have lower SGLT1 transport activity. Transepithelial PSGLT1 across Caco-2 cells from DSMZ showed that PSGLT1 likely accounts for approximately 97% of absorptive α-MDG Papp(a-b). In conclusion, Caco-2 cells from DSMZ provide a robust in vitro model for studying SGLT1-mediated uptake and transport - over multiple cell passages and independent cell stock thawings.

Original languageEnglish
JournalJournal of Pharmaceutical Sciences
Volume106
Issue number9
Pages (from-to)2664-2670
ISSN0022-3549
DOIs
Publication statusPublished - 2017

Fingerprint

Caco-2 Cells
Cell Line
Food
Pharmaceutical Preparations

Keywords

  • Journal Article

Cite this

@article{3099d7374b0f4668bca19ba7c976208a,
title = "SGLT1-mediated transport in Caco-2 cells is highly dependent on cell bank origin",
abstract = "The Caco-2 cell line is a well-established in vitro model for studying transport phenomena for prediction of intestinal nutrient and drug absorption. However, for substances depending on transporters such predictions are complicated due to variable transporter expression and limited knowledge about transporter function during multiple cell passaging and cell thawings. In the case of SGLT1, a key transporter of oral absorption of D-glucose, one reason for compromised prediction could be inadequate expression of SGLT1 in Caco-2 cells and thereby limited sensitivity in the determination of SGLT1-mediated permeability (PSGLT1). Here, the objective was to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate, α-MDG, in Caco-2 cells was shown to be highly dependent on cell bank origin. The most robust and reliable SGLT1 functionality was identified in Caco-2 cells from DSMZ, whereas cells from ATCC and ECACC have lower SGLT1 transport activity. Transepithelial PSGLT1 across Caco-2 cells from DSMZ showed that PSGLT1 likely accounts for approximately 97{\%} of absorptive α-MDG Papp(a-b). In conclusion, Caco-2 cells from DSMZ provide a robust in vitro model for studying SGLT1-mediated uptake and transport - over multiple cell passages and independent cell stock thawings.",
keywords = "Journal Article",
author = "B Steffansen and Maria Pedersen and Laghmoch, {A M} and Nielsen, {C U}",
note = "Copyright {\circledC} 2017. Published by Elsevier Inc.",
year = "2017",
doi = "10.1016/j.xphs.2017.04.033",
language = "English",
volume = "106",
pages = "2664--2670",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "Elsevier",
number = "9",

}

SGLT1-mediated transport in Caco-2 cells is highly dependent on cell bank origin. / Steffansen, B; Pedersen, Maria ; Laghmoch, A M; Nielsen, C U.

In: Journal of Pharmaceutical Sciences, Vol. 106, No. 9, 2017, p. 2664-2670.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - SGLT1-mediated transport in Caco-2 cells is highly dependent on cell bank origin

AU - Steffansen, B

AU - Pedersen, Maria

AU - Laghmoch, A M

AU - Nielsen, C U

N1 - Copyright © 2017. Published by Elsevier Inc.

PY - 2017

Y1 - 2017

N2 - The Caco-2 cell line is a well-established in vitro model for studying transport phenomena for prediction of intestinal nutrient and drug absorption. However, for substances depending on transporters such predictions are complicated due to variable transporter expression and limited knowledge about transporter function during multiple cell passaging and cell thawings. In the case of SGLT1, a key transporter of oral absorption of D-glucose, one reason for compromised prediction could be inadequate expression of SGLT1 in Caco-2 cells and thereby limited sensitivity in the determination of SGLT1-mediated permeability (PSGLT1). Here, the objective was to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate, α-MDG, in Caco-2 cells was shown to be highly dependent on cell bank origin. The most robust and reliable SGLT1 functionality was identified in Caco-2 cells from DSMZ, whereas cells from ATCC and ECACC have lower SGLT1 transport activity. Transepithelial PSGLT1 across Caco-2 cells from DSMZ showed that PSGLT1 likely accounts for approximately 97% of absorptive α-MDG Papp(a-b). In conclusion, Caco-2 cells from DSMZ provide a robust in vitro model for studying SGLT1-mediated uptake and transport - over multiple cell passages and independent cell stock thawings.

AB - The Caco-2 cell line is a well-established in vitro model for studying transport phenomena for prediction of intestinal nutrient and drug absorption. However, for substances depending on transporters such predictions are complicated due to variable transporter expression and limited knowledge about transporter function during multiple cell passaging and cell thawings. In the case of SGLT1, a key transporter of oral absorption of D-glucose, one reason for compromised prediction could be inadequate expression of SGLT1 in Caco-2 cells and thereby limited sensitivity in the determination of SGLT1-mediated permeability (PSGLT1). Here, the objective was to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate, α-MDG, in Caco-2 cells was shown to be highly dependent on cell bank origin. The most robust and reliable SGLT1 functionality was identified in Caco-2 cells from DSMZ, whereas cells from ATCC and ECACC have lower SGLT1 transport activity. Transepithelial PSGLT1 across Caco-2 cells from DSMZ showed that PSGLT1 likely accounts for approximately 97% of absorptive α-MDG Papp(a-b). In conclusion, Caco-2 cells from DSMZ provide a robust in vitro model for studying SGLT1-mediated uptake and transport - over multiple cell passages and independent cell stock thawings.

KW - Journal Article

U2 - 10.1016/j.xphs.2017.04.033

DO - 10.1016/j.xphs.2017.04.033

M3 - Journal article

VL - 106

SP - 2664

EP - 2670

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 9

ER -