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

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

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Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, Japan.
Department of Cardiovascular Surgery, Tokyo Women's Medical University, Tokyo, Japan.


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.

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Conflict of interest statement

There are potential competing interests. Teruo Okano is a founder and a member of the board of CellSeed Inc. to which a cell sheet-related patent family (THERAPEUTIC SUBSTANCE DELIVERY DEVICE AND THERAPEUTIC SUBSTANCE DELIVERY KIT, WO/2017/043600) is licensed by Tokyo Women’s Medical University. Tatsuya Shimizu is a member of the scientific advisory board of CellSeed Inc. Teruo Okano and Tatsuya Shimizu are shareholders of CellSeed Inc. Tokyo Women’s Medical University receives a research fund from CellSeed Inc. for the practical application of cell sheet engineering, and a research fund from Panasonic Corporation for the establishment of noninvasive evaluation method of three-dimensional tissues. Teruo Okano, Tatsuya Shimizu, and Katsuhisa Matsuura are inventors of the bioreactor system for differentiation culture of pluripotent stem cells, the patent of which is held by Able Co. and Tokyo Women’s Medical University (CELL CULTURE APPARATUS AND CELL CULTURE METHOD USING SAME, US9574165B2). These competing interests do not alter our adherence to PLOS ONE policies on sharing data and materials.

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