PMID- 32629159
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20210715
IS  - 1873-488X (Electronic)
IS  - 1056-8719 (Linking)
VI  - 105
DP  - 2020 Sep
TI  - Inotropic assessment in engineered 3D cardiac tissues using human induced 
      pluripotent stem cell-derived cardiomyocytes in the Biowire(TM) II platform.
PG  - 106886
LID - S1056-8719(20)30215-X [pii]
LID - 10.1016/j.vascn.2020.106886 [doi]
AB  - To develop therapeutics for cardiovascular disease, especially heart failure, 
      translational models for assessing cardiac contractility are necessary for 
      preclinical target validation and lead optimization. The availability of stem 
      cell-derived cardiomyocytes (SC-CM) has generated a great opportunity in 
      developing new in-vitro models for assessing cardiac contractility. However, the 
      immature phenotype of SC-CM is a well-recognized limitation in inotropic 
      evaluation, especially regarding the lack of or diminished positive inotropic 
      response to beta-adrenergic agonists. Recent development of 3D engineered cardiac 
      tissues (ECTs) using human induced pluripotent stem cell derived-cardiomyocytes 
      (hiPSC-CM) in the Biowire(TM) II platform has shown improved maturation. To 
      evaluate their suitability to detect drug-induced changes in cardiac 
      contractility, positive inotropes with diverse mechanisms, including beta-adrenergic 
      agonists, PDE3 inhibitors, Ca(2+)-sensitizers, myosin and troponin activators, 
      and an apelin receptor agonist, were tested blindly. A total of 8 compounds were 
      evaluated, including dobutamine, milrinone, pimobendan, levosimendan, omecamtiv 
      mecarbil, AMG1, AMG2, and pyr-apelin-13. Contractility was evaluated by analyzing 
      the amplitude, velocity and duration of contraction and relaxation. All tested 
      agents, except pyr-apelin-13, increased contractility by increasing the amplitude 
      of contraction and velocity. In addition, myosin and troponin activators increase 
      contraction duration. These results indicate that ECTs generated in the 
      Biowire(TM) II platform can identify inotropes with different mechanisms and 
      provides a human-based in-vitro model for evaluating potential therapeutics.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Qu, Yusheng
AU  - Qu Y
AD  - Amgen Research, Translational Safety & Bioanalytical Sciences, Thousand Oaks, CA, 
      USA. Electronic address: yqu@amgen.com.
FAU - Feric, Nicole
AU  - Feric N
AD  - TARA Biosystems, New York, NY, USA.
FAU - Pallotta, Isabella
AU  - Pallotta I
AD  - TARA Biosystems, New York, NY, USA.
FAU - Singh, Rishabh
AU  - Singh R
AD  - TARA Biosystems, New York, NY, USA.
FAU - Sobbi, Rooz
AU  - Sobbi R
AD  - TARA Biosystems, New York, NY, USA.
FAU - Vargas, Hugo M
AU  - Vargas HM
AD  - Amgen Research, Translational Safety & Bioanalytical Sciences, Thousand Oaks, CA, 
      USA.
LA  - eng
PT  - Journal Article
DEP - 20200703
PL  - United States
TA  - J Pharmacol Toxicol Methods
JT  - Journal of pharmacological and toxicological methods
JID - 9206091
SB  - IM
MH  - Cells, Cultured
MH  - Humans
MH  - Induced Pluripotent Stem Cells/*cytology
MH  - Myocardial Contraction/physiology
MH  - Myocytes, Cardiac/*cytology
MH  - Regeneration/*physiology
MH  - Tissue Scaffolds/*chemistry
OTO - NOTNLM
OT  - 3D
OT  - Cardiac contractility
OT  - Engineered cardiac tissue
OT  - Inotropes
OT  - hiPSC-CM
COIS- Declaration of Competing Interest Amgen Inc. provided study funding. YQ and HMV 
      are employees and shareholders of Amgen Inc. NF, IP, RS, and RS are employees and 
      shareholders of TARA Biosystems Inc.
EDAT- 2020/07/07 06:00
MHDA- 2021/07/16 06:00
CRDT- 2020/07/07 06:00
PHST- 2020/02/20 00:00 [received]
PHST- 2020/05/22 00:00 [revised]
PHST- 2020/06/08 00:00 [accepted]
PHST- 2020/07/07 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
PHST- 2020/07/07 06:00 [entrez]
AID - S1056-8719(20)30215-X [pii]
AID - 10.1016/j.vascn.2020.106886 [doi]
PST - ppublish
SO  - J Pharmacol Toxicol Methods. 2020 Sep;105:106886. doi: 
      10.1016/j.vascn.2020.106886. Epub 2020 Jul 3.