PMID- 37421087
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2072-666X (Print)
IS  - 2072-666X (Electronic)
IS  - 2072-666X (Linking)
VI  - 14
IP  - 4
DP  - 2023 Apr 14
TI  - Importance of Spatial Arrangement of Cardiomyocyte Network for Precise and Stable 
      On-Chip Predictive Cardiotoxicity Measurement.
LID - 10.3390/mi14040854 [doi]
LID - 854
AB  - One of the advantages of human stem cell-derived cell-based preclinical screening 
      is the reduction of the false negative/positive misjudgment of lead compounds for 
      predicting their effectiveness and risks during the early stage of development. 
      However, as the community effect of cells was neglected in the conventional 
      single cell-based in vitro screening, the potential difference in results caused 
      by the cell number and their spatial arrangement differences has not yet been 
      sufficiently evaluated. Here, we have investigated the effect of the community 
      size and spatial arrangement difference for cardiomyocyte network response 
      against the proarrhythmic compounds from the viewpoint of in vitro 
      cardiotoxicity. Using three different typical types of cell networks of 
      cardiomyocytes, small cluster, large square sheet, and large closed-loop sheet 
      were formed in shaped agarose microchambers fabricated on a multielectrode array 
      chip simultaneously, and their responses were compared against the proarrhythmic 
      compound, E-4031. The interspike intervals (ISIs) in large square sheets and 
      closed-loop sheets were durable and maintained stable against E-4031 even at a 
      high dose of 100 nM. In contrast, those in the small cluster, which fluctuated 
      even without E-4031, acquired stable beating reflecting the antiarrhythmic 
      efficacy of E-4031 from a 10 nM medium dose administration. The repolarization 
      index, field potential duration (FPD), was prolonged in closed-loop sheets with 
      10 nM E-4031, even though small clusters and large sheets remained normal at this 
      concentration. Moreover, FPDs of large sheets were the most durable against 
      E-4031 among the three geometries of cardiomyocyte networks. The results showed 
      the apparent spatial arrangement dependence on the stability of their interspike 
      intervals, and FPD prolongation, indicating the importance of the geometry 
      control of cell networks for representing the appropriate response of 
      cardiomyocytes against the adequate amount of compounds for in vitro ion channel 
      measurement.
FAU - Sakamoto, Kazufumi
AU  - Sakamoto K
AD  - Department of Pure and Applied Physics, Graduate School of Advanced Science and 
      Engineering, Waseda University, Tokyo 169-8555, Japan.
FAU - Matsumoto, Suguru
AU  - Matsumoto S
AD  - Department of Pure and Applied Physics, Graduate School of Advanced Science and 
      Engineering, Waseda University, Tokyo 169-8555, Japan.
FAU - Abe, Nanami
AU  - Abe N
AD  - Department of Pure and Applied Physics, Graduate School of Advanced Science and 
      Engineering, Waseda University, Tokyo 169-8555, Japan.
FAU - Sentoku, Mitsuru
AU  - Sentoku M
AD  - Department of Pure and Applied Physics, Graduate School of Advanced Science and 
      Engineering, Waseda University, Tokyo 169-8555, Japan.
FAU - Yasuda, Kenji
AU  - Yasuda K
AUID- ORCID: 0000-0002-1433-4509
AD  - Department of Pure and Applied Physics, Graduate School of Advanced Science and 
      Engineering, Waseda University, Tokyo 169-8555, Japan.
AD  - Department of Physics, School of Advanced Science and Engineering, Waseda 
      University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan.
LA  - eng
GR  - 22K18955/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20230414
PL  - Switzerland
TA  - Micromachines (Basel)
JT  - Micromachines
JID - 101640903
PMC - PMC10143097
OTO - NOTNLM
OT  - cardiomyocyte
OT  - community effect
OT  - geometry dependence
OT  - predictive toxicity
OT  - synchronization
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/08 10:42
MHDA- 2023/07/08 10:43
PMCR- 2023/04/14
CRDT- 2023/07/08 01:13
PHST- 2023/03/31 00:00 [received]
PHST- 2023/04/13 00:00 [revised]
PHST- 2023/04/13 00:00 [accepted]
PHST- 2023/07/08 10:43 [medline]
PHST- 2023/07/08 10:42 [pubmed]
PHST- 2023/07/08 01:13 [entrez]
PHST- 2023/04/14 00:00 [pmc-release]
AID - mi14040854 [pii]
AID - micromachines-14-00854 [pii]
AID - 10.3390/mi14040854 [doi]
PST - epublish
SO  - Micromachines (Basel). 2023 Apr 14;14(4):854. doi: 10.3390/mi14040854.