Contractile force measurement of human induced pluripotent stem cell-derived cardiac cell sheet-tissue

PLoS One. 2018 May 23;13(5):e0198026. doi: 10.1371/journal.pone.0198026. eCollection 2018.

Abstract

We have developed our original tissue engineering technology "cell sheet engineering" utilizing temperature-responsive culture dishes. The cells are confluently grown on a temperature-responsive culture dish and can be harvested as a cell sheet by lowering temperature without enzymatic digestion. Cell sheets are high-cell-density tissues similar to actual living tissues, maintaining their structure and function. Based on this "cell sheet engineering", we are trying to create functional cardiac tissues from human induced pluripotent stem cells, for regenerative therapy and in vitro drug testing. Toward this purpose, it is necessary to evaluate the contractility of engineered cardiac cell sheets. Therefore, in the present study, we developed a contractile force measurement system and evaluated the contractility of human iPSC-derived cardiac cell sheet-tissues. By attaching the cardiac cell sheets on fibrin gel sheets, we created dynamically beating cardiac cell sheet-tissues. They were mounted to the force measurement system and the contractile force was measured stably and clearly. The absolute values of contractile force were around 1 mN, and the mean force value per cross-sectional area was 3.3 mN/mm2. These values are equivalent to or larger than many previously reported values, indicating the functionality of our engineered cardiac cell sheets. We also confirmed that both the contractile force and beating rate were significantly increased by the administration of adrenaline, which are the physiologically relevant responses for cardiac tissues. In conclusion, the force measurement system developed in the present study is valuable for the evaluation of engineered cardiac cell sheet-tissues, and for in vitro drug testing as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Epinephrine / pharmacology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Muscle Contraction* / drug effects
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Tissue Engineering

Substances

  • Epinephrine

Grants and funding

This work was supported by Formation of Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science and Technology "Innovation Center for Fusion of Advanced Technologies to Realize Regenerative Medicines" from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (http://www.mext.go.jp/en/). This work was also supported by Japan Agency for Medical Research and Development (AMED, https://www.amed.go.jp/en/index.html) under Grant Number JP17im0302706.