PMID- 35385754
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220504
IS  - 2211-1247 (Electronic)
VI  - 39
IP  - 1
DP  - 2022 Apr 5
TI  - Population-based high-throughput toxicity screen of human iPSC-derived 
      cardiomyocytes and neurons.
PG  - 110643
LID - S2211-1247(22)00395-3 [pii]
LID - 10.1016/j.celrep.2022.110643 [doi]
AB  - In this study, we establish a population-based human induced pluripotent stem 
      cell (hiPSC) drug screening platform for toxicity assessment. After recruiting 
      1,000 healthy donors and screening for high-frequency human leukocyte antigen 
      (HLA) haplotypes, we identify 13 HLA-homozygous "super donors" to represent the 
      population. These "super donors" are also expected to represent at least 
      477,611,135 of the global population. By differentiating these representative 
      hiPSCs into cardiomyocytes and neurons we show their utility in a high-throughput 
      toxicity screen. To validate hit compounds, we demonstrate dose-dependent 
      toxicity of the hit compounds and assess functional modulation. We also show 
      reproducible in vivo drug toxicity results using mouse models with select hit 
      compounds. This study shows the feasibility of using a population-based hiPSC 
      drug screening platform to assess cytotoxicity, which can be used as an 
      innovative tool to study inter-population differences in drug toxicity and 
      adverse drug reactions in drug discovery applications.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Huang, Ching Ying
AU  - Huang CY
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Nicholson, Martin W
AU  - Nicholson MW
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Wang, Jyun Yuan
AU  - Wang JY
AD  - Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
FAU - Ting, Chien Yu
AU  - Ting CY
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Tsai, Ming Heng
AU  - Tsai MH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Cheng, Yu Che
AU  - Cheng YC
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Liu, Chun Lin
AU  - Liu CL
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Chan, Darien Z H
AU  - Chan DZH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Lee, Yi Chan
AU  - Lee YC
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Hsu, Ching Chuan
AU  - Hsu CC
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Hsu, Yu Hung
AU  - Hsu YH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Yang, Chiou Fong
AU  - Yang CF
AD  - Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan.
FAU - Chang, Cindy M C
AU  - Chang CMC
AD  - Cardiovascular Physiology Core Facility, Department of Medicine, University of 
      Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Ruan, Shu Chian
AU  - Ruan SC
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Lin, Po Ju
AU  - Lin PJ
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Lin, Jen Hao
AU  - Lin JH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Chen, Li Lun
AU  - Chen LL
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Hsieh, Marvin L
AU  - Hsieh ML
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; 
      Cardiovascular Physiology Core Facility, Department of Medicine, University of 
      Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Cheng, Yuan Yuan
AU  - Cheng YY
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Hsu, Wan Tseng
AU  - Hsu WT
AD  - School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, 
      Taiwan.
FAU - Lin, Yi Ling
AU  - Lin YL
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Chen, Chien Hsiun
AU  - Chen CH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
FAU - Hsu, Yu Hsiang
AU  - Hsu YH
AD  - Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan.
FAU - Wu, Ying Ta
AU  - Wu YT
AD  - Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
FAU - Hacker, Timothy A
AU  - Hacker TA
AD  - Cardiovascular Physiology Core Facility, Department of Medicine, University of 
      Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Wu, Joseph C
AU  - Wu JC
AD  - Stanford Cardiovascular Institute, Stanford University School of Medicine, 
      Stanford, CA 94305, USA.
FAU - Kamp, Timothy J
AU  - Kamp TJ
AD  - Department of Medicine and Stem Cell and Regenerative Medicine Center, University 
      of Wisconsin-Madison, Madison, WI 53705, USA.
FAU - Hsieh, Patrick C H
AU  - Hsieh PCH
AD  - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Department 
      of Medicine and Stem Cell and Regenerative Medicine Center, University of 
      Wisconsin-Madison, Madison, WI 53705, USA; Institute of Medical Genomics and 
      Proteomics and Institute of Clinical Medicine, National Taiwan University, Taipei 
      106, Taiwan. Electronic address: phsieh@ibms.sinica.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
SB  - IM
MH  - Animals
MH  - Cardiotoxicity
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Humans
MH  - *Induced Pluripotent Stem Cells
MH  - Mice
MH  - Myocytes, Cardiac
MH  - Neurons
OTO - NOTNLM
OT  - CP: Stem cell research
OT  - cardiomyocyte
OT  - drug screening
OT  - human leukocyte antigen
OT  - human-induced pluripotent stem cell
OT  - neuron
OT  - toxicity
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2022/04/07 06:00
MHDA- 2022/04/09 06:00
CRDT- 2022/04/06 20:05
PHST- 2021/07/06 00:00 [received]
PHST- 2022/01/13 00:00 [revised]
PHST- 2022/03/16 00:00 [accepted]
PHST- 2022/04/06 20:05 [entrez]
PHST- 2022/04/07 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
AID - S2211-1247(22)00395-3 [pii]
AID - 10.1016/j.celrep.2022.110643 [doi]
PST - ppublish
SO  - Cell Rep. 2022 Apr 5;39(1):110643. doi: 10.1016/j.celrep.2022.110643.