Liver-immune coculture array predicts drug-metabolism-induced skin sensitization

Lor Huai Chong; Huan Li; Isaac Wetzel; Hansang Cho; Yi Chin Toh

Liver-immune coculture array predicts drug-metabolism-induced skin sensitization

Lor Huai Chong
, Huan Li
, Isaac Wetzel
, Hansang Cho
, Yi Chin Toh

Research output: Chapter in Book/Report/Conference proceeding › Conference Paper › Other

Abstract

We report a novel liver-immune coculture array that recapitulate the tandem hepatic drug metabolism and immune activation processes which can accurately predict the skin sensitization potential of drugs administered into the systemic circulation. This was accomplished by designing a compartmentalized microfluidic array that supported HepaRG-derived-hepatocytes-spheroids(HHS) (liver) with U937 (immune) coculture and maintained their respective functions, while promoting efficient transport and accumulation of drug reactive metabolites to trigger a robust APC activation response. We demonstrated that our liver-immune coculture array could more consistently and reliably distinguish 3 paradigm skin sensitizing drugs from a non-skin sensitizer than the conventional Transwell system.

Original language	English
Title of host publication	22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018
Publisher	Chemical and Biological Microsystems Society
Pages	167-170
Number of pages	4
ISBN (Electronic)	9781510897571
Publication status	Published - 2018
Externally published	Yes
Event	International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2018) - Kaohsiung, Taiwan Duration: 11 Nov 2018 → 15 Nov 2018 Conference number: 22nd

Conference

Conference	International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2018)
Abbreviated title	MicroTAS 2018
Country/Territory	Taiwan
City	Kaohsiung
Period	11/11/18 → 15/11/18

Keywords

Compartmentalized microfluidic
HepaRG
Liver-immune coculture array
Systemic drugs induced skin sensitization
U937

Cite this

@inproceedings{0eb284f8b749417a9dcfae3c3a4c2485,

title = "Liver-immune coculture array predicts drug-metabolism-induced skin sensitization",

abstract = "We report a novel liver-immune coculture array that recapitulate the tandem hepatic drug metabolism and immune activation processes which can accurately predict the skin sensitization potential of drugs administered into the systemic circulation. This was accomplished by designing a compartmentalized microfluidic array that supported HepaRG-derived-hepatocytes-spheroids(HHS) (liver) with U937 (immune) coculture and maintained their respective functions, while promoting efficient transport and accumulation of drug reactive metabolites to trigger a robust APC activation response. We demonstrated that our liver-immune coculture array could more consistently and reliably distinguish 3 paradigm skin sensitizing drugs from a non-skin sensitizer than the conventional Transwell system.",

keywords = "Compartmentalized microfluidic, HepaRG, Liver-immune coculture array, Systemic drugs induced skin sensitization, U937",

author = "Chong, \{Lor Huai\} and Huan Li and Isaac Wetzel and Hansang Cho and Toh, \{Yi Chin\}",

note = "Funding Information: This study was supported by funding from Singapore Ministry of Education (R-397-000-215-112, R-397-000-253-112, R-397-000-242-112), Singapore Institute for Neurotechnology (R-719-004-100-305), BIGHEART and NUS Tissue Engineering Program (NUSTEP). LHC is a NUS Research Scholar. Publisher Copyright: Copyright{\textcopyright} (2018) by Chemical and Biological Microsystems Society.All rights reserved.; International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2018), MicroTAS 2018 ; Conference date: 11-11-2018 Through 15-11-2018",

year = "2018",

language = "English",

pages = "167--170",

booktitle = "22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018",

publisher = "Chemical and Biological Microsystems Society",

address = "United States of America",

}

Chong, LH, Li, H, Wetzel, I, Cho, H & Toh, YC 2018, Liver-immune coculture array predicts drug-metabolism-induced skin sensitization. in 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018. Chemical and Biological Microsystems Society, pp. 167-170, International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2018), Kaohsiung, Taiwan, 11/11/18.

Liver-immune coculture array predicts drug-metabolism-induced skin sensitization. / Chong, Lor Huai; Li, Huan; Wetzel, Isaac et al.
22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018. Chemical and Biological Microsystems Society, 2018. p. 167-170.

Research output: Chapter in Book/Report/Conference proceeding › Conference Paper › Other

TY - GEN

T1 - Liver-immune coculture array predicts drug-metabolism-induced skin sensitization

AU - Chong, Lor Huai

AU - Li, Huan

AU - Wetzel, Isaac

AU - Cho, Hansang

AU - Toh, Yi Chin

N1 - Conference code: 22nd

PY - 2018

Y1 - 2018

N2 - We report a novel liver-immune coculture array that recapitulate the tandem hepatic drug metabolism and immune activation processes which can accurately predict the skin sensitization potential of drugs administered into the systemic circulation. This was accomplished by designing a compartmentalized microfluidic array that supported HepaRG-derived-hepatocytes-spheroids(HHS) (liver) with U937 (immune) coculture and maintained their respective functions, while promoting efficient transport and accumulation of drug reactive metabolites to trigger a robust APC activation response. We demonstrated that our liver-immune coculture array could more consistently and reliably distinguish 3 paradigm skin sensitizing drugs from a non-skin sensitizer than the conventional Transwell system.

AB - We report a novel liver-immune coculture array that recapitulate the tandem hepatic drug metabolism and immune activation processes which can accurately predict the skin sensitization potential of drugs administered into the systemic circulation. This was accomplished by designing a compartmentalized microfluidic array that supported HepaRG-derived-hepatocytes-spheroids(HHS) (liver) with U937 (immune) coculture and maintained their respective functions, while promoting efficient transport and accumulation of drug reactive metabolites to trigger a robust APC activation response. We demonstrated that our liver-immune coculture array could more consistently and reliably distinguish 3 paradigm skin sensitizing drugs from a non-skin sensitizer than the conventional Transwell system.

KW - Compartmentalized microfluidic

KW - HepaRG

KW - Liver-immune coculture array

KW - Systemic drugs induced skin sensitization

KW - U937

UR - https://www.scopus.com/pages/publications/85079905160

M3 - Conference Paper

AN - SCOPUS:85079905160

SP - 167

EP - 170

BT - 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018

PB - Chemical and Biological Microsystems Society

T2 - International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2018)

Y2 - 11 November 2018 through 15 November 2018

ER -

Liver-immune coculture array predicts drug-metabolism-induced skin sensitization

Abstract

Conference

Keywords

Other files and links

Cite this